Source 1primary paper2017Genome biology
Toolkit/SpCas9-HF1
SpCas9-HF1
Taxonomy: Mechanism Branch / Component. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
SpCas9-HF1 is an engineered high-fidelity Streptococcus pyogenes Cas9 nuclease variant evaluated in comparative studies of increased-specificity SpCas9 enzymes. It is used for genome cleavage applications in which target-dependent optimization of specificity is required.
Usefulness & Problems
Why this is useful
SpCas9-HF1 is useful as part of a panel of increased-fidelity SpCas9 nucleases for selecting a nuclease-guide configuration that maximizes cleavage specificity at a given target. The cited study indicates that highest-specificity editing is achieved by matching each target with an appropriate high-fidelity nuclease rather than assuming one variant is optimal for all sites.
Source:
for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease
Problem solved
This tool helps address the problem that genome editing specificity is strongly target dependent and that no single high-fidelity SpCas9 variant is uniformly best across targets. It therefore supports target-by-target optimization of nuclease choice for specific DNA cleavage.
Source:
for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease
Problem links
Need conditional recombination or state switching
DerivedSpCas9-HF1 is a high-fidelity Streptococcus pyogenes Cas9 nuclease variant discussed in comparative studies of increased-specificity SpCas9 enzymes. The cited evidence places it within a set of engineered nucleases used for target-dependent optimization of genome cleavage specificity.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Component: A low-level protein part used inside a larger architecture that realizes a mechanism.
Techniques
No technique tags yet.
Target processes
recombinationImplementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationoperating role: actuatoroperating role: regulatorswitch architecture: cleavage
The cited evidence supports using SpCas9-HF1 in a target-matched selection workflow among high-fidelity SpCas9 variants. It also indicates that 5' guide extensions can affect activity, with a matching 5' G extension being more detrimental than a mismatching 5' G extension for increased-fidelity nucleases; no additional construct, delivery, or cofactor details are provided in the supplied evidence.
The supplied evidence does not provide SpCas9-HF1-specific quantitative performance data, mutation identities, or direct measurements of on-target versus off-target editing. It also states that no single high-fidelity SpCas9 nuclease is generally superior in fidelity across targets, limiting any claim of universal advantage for SpCas9-HF1.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
For the increased-fidelity nucleases, a matching 5' G extension is more detrimental to activity than a mismatching 5' G extension.
a matching 5' G extension being more detrimental to their activities than a mismatching one
For the increased-fidelity nucleases, a matching 5' G extension is more detrimental to activity than a mismatching 5' G extension.
a matching 5' G extension being more detrimental to their activities than a mismatching one
For the increased-fidelity nucleases, a matching 5' G extension is more detrimental to activity than a mismatching 5' G extension.
a matching 5' G extension being more detrimental to their activities than a mismatching one
For the increased-fidelity nucleases, a matching 5' G extension is more detrimental to activity than a mismatching 5' G extension.
a matching 5' G extension being more detrimental to their activities than a mismatching one
For the increased-fidelity nucleases, a matching 5' G extension is more detrimental to activity than a mismatching 5' G extension.
a matching 5' G extension being more detrimental to their activities than a mismatching one
For the increased-fidelity nucleases, a matching 5' G extension is more detrimental to activity than a mismatching 5' G extension.
a matching 5' G extension being more detrimental to their activities than a mismatching one
For the increased-fidelity nucleases, a matching 5' G extension is more detrimental to activity than a mismatching 5' G extension.
a matching 5' G extension being more detrimental to their activities than a mismatching one
For the increased-fidelity nucleases, a matching 5' G extension is more detrimental to activity than a mismatching 5' G extension.
a matching 5' G extension being more detrimental to their activities than a mismatching one
For the increased-fidelity nucleases, a matching 5' G extension is more detrimental to activity than a mismatching 5' G extension.
a matching 5' G extension being more detrimental to their activities than a mismatching one
For the increased-fidelity nucleases, a matching 5' G extension is more detrimental to activity than a mismatching 5' G extension.
a matching 5' G extension being more detrimental to their activities than a mismatching one
For the increased-fidelity nucleases, a matching 5' G extension is more detrimental to activity than a mismatching 5' G extension.
a matching 5' G extension being more detrimental to their activities than a mismatching one
For the increased-fidelity nucleases, a matching 5' G extension is more detrimental to activity than a mismatching 5' G extension.
a matching 5' G extension being more detrimental to their activities than a mismatching one
For the increased-fidelity nucleases, a matching 5' G extension is more detrimental to activity than a mismatching 5' G extension.
a matching 5' G extension being more detrimental to their activities than a mismatching one
For the increased-fidelity nucleases, a matching 5' G extension is more detrimental to activity than a mismatching 5' G extension.
a matching 5' G extension being more detrimental to their activities than a mismatching one
For the increased-fidelity nucleases, a matching 5' G extension is more detrimental to activity than a mismatching 5' G extension.
a matching 5' G extension being more detrimental to their activities than a mismatching one
For the increased-fidelity nucleases, a matching 5' G extension is more detrimental to activity than a mismatching 5' G extension.
a matching 5' G extension being more detrimental to their activities than a mismatching one
For the increased-fidelity nucleases, a matching 5' G extension is more detrimental to activity than a mismatching 5' G extension.
a matching 5' G extension being more detrimental to their activities than a mismatching one
For highest-specificity cleavage, each target should be matched with an appropriate high-fidelity nuclease.
for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease
For highest-specificity cleavage, each target should be matched with an appropriate high-fidelity nuclease.
for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease
For highest-specificity cleavage, each target should be matched with an appropriate high-fidelity nuclease.
for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease
For highest-specificity cleavage, each target should be matched with an appropriate high-fidelity nuclease.
for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease
For highest-specificity cleavage, each target should be matched with an appropriate high-fidelity nuclease.
for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease
For highest-specificity cleavage, each target should be matched with an appropriate high-fidelity nuclease.
for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease
For highest-specificity cleavage, each target should be matched with an appropriate high-fidelity nuclease.
for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease
For highest-specificity cleavage, each target should be matched with an appropriate high-fidelity nuclease.
for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease
For highest-specificity cleavage, each target should be matched with an appropriate high-fidelity nuclease.
for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease
For highest-specificity cleavage, each target should be matched with an appropriate high-fidelity nuclease.
for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease
For highest-specificity cleavage, each target should be matched with an appropriate high-fidelity nuclease.
for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease
For highest-specificity cleavage, each target should be matched with an appropriate high-fidelity nuclease.
for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease
For highest-specificity cleavage, each target should be matched with an appropriate high-fidelity nuclease.
for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease
For highest-specificity cleavage, each target should be matched with an appropriate high-fidelity nuclease.
for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease
For highest-specificity cleavage, each target should be matched with an appropriate high-fidelity nuclease.
for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease
For highest-specificity cleavage, each target should be matched with an appropriate high-fidelity nuclease.
for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease
For highest-specificity cleavage, each target should be matched with an appropriate high-fidelity nuclease.
for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease
No single high-fidelity SpCas9 nuclease variant is generally superior in fidelity across targets.
No single nuclease variant shows generally superior fidelity
No single high-fidelity SpCas9 nuclease variant is generally superior in fidelity across targets.
No single nuclease variant shows generally superior fidelity
No single high-fidelity SpCas9 nuclease variant is generally superior in fidelity across targets.
No single nuclease variant shows generally superior fidelity
No single high-fidelity SpCas9 nuclease variant is generally superior in fidelity across targets.
No single nuclease variant shows generally superior fidelity
No single high-fidelity SpCas9 nuclease variant is generally superior in fidelity across targets.
No single nuclease variant shows generally superior fidelity
No single high-fidelity SpCas9 nuclease variant is generally superior in fidelity across targets.
No single nuclease variant shows generally superior fidelity
No single high-fidelity SpCas9 nuclease variant is generally superior in fidelity across targets.
No single nuclease variant shows generally superior fidelity
No single high-fidelity SpCas9 nuclease variant is generally superior in fidelity across targets.
No single nuclease variant shows generally superior fidelity
No single high-fidelity SpCas9 nuclease variant is generally superior in fidelity across targets.
No single nuclease variant shows generally superior fidelity
No single high-fidelity SpCas9 nuclease variant is generally superior in fidelity across targets.
No single nuclease variant shows generally superior fidelity
No single high-fidelity SpCas9 nuclease variant is generally superior in fidelity across targets.
No single nuclease variant shows generally superior fidelity
No single high-fidelity SpCas9 nuclease variant is generally superior in fidelity across targets.
No single nuclease variant shows generally superior fidelity
No single high-fidelity SpCas9 nuclease variant is generally superior in fidelity across targets.
No single nuclease variant shows generally superior fidelity
No single high-fidelity SpCas9 nuclease variant is generally superior in fidelity across targets.
No single nuclease variant shows generally superior fidelity
No single high-fidelity SpCas9 nuclease variant is generally superior in fidelity across targets.
No single nuclease variant shows generally superior fidelity
No single high-fidelity SpCas9 nuclease variant is generally superior in fidelity across targets.
No single nuclease variant shows generally superior fidelity
No single high-fidelity SpCas9 nuclease variant is generally superior in fidelity across targets.
No single nuclease variant shows generally superior fidelity
HeFSpCas9 variants were generated by combining mutations from eSpCas9 and SpCas9-HF1.
we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1
HeFSpCas9 variants were generated by combining mutations from eSpCas9 and SpCas9-HF1.
we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1
HeFSpCas9 variants were generated by combining mutations from eSpCas9 and SpCas9-HF1.
we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1
HeFSpCas9 variants were generated by combining mutations from eSpCas9 and SpCas9-HF1.
we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1
HeFSpCas9 variants were generated by combining mutations from eSpCas9 and SpCas9-HF1.
we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1
HeFSpCas9 variants were generated by combining mutations from eSpCas9 and SpCas9-HF1.
we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1
HeFSpCas9 variants were generated by combining mutations from eSpCas9 and SpCas9-HF1.
we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1
HeFSpCas9 variants were generated by combining mutations from eSpCas9 and SpCas9-HF1.
we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1
HeFSpCas9 variants were generated by combining mutations from eSpCas9 and SpCas9-HF1.
we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1
HeFSpCas9 variants were generated by combining mutations from eSpCas9 and SpCas9-HF1.
we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1
HeFSpCas9 variants were generated by combining mutations from eSpCas9 and SpCas9-HF1.
we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1
HeFSpCas9 variants were generated by combining mutations from eSpCas9 and SpCas9-HF1.
we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1
HeFSpCas9 variants were generated by combining mutations from eSpCas9 and SpCas9-HF1.
we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1
HeFSpCas9 variants were generated by combining mutations from eSpCas9 and SpCas9-HF1.
we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1
HeFSpCas9 variants were generated by combining mutations from eSpCas9 and SpCas9-HF1.
we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1
HeFSpCas9 variants were generated by combining mutations from eSpCas9 and SpCas9-HF1.
we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1
HeFSpCas9 variants were generated by combining mutations from eSpCas9 and SpCas9-HF1.
we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1
Mutations in the increased-fidelity SpCas9 variants may reduce cleavage without reducing DNA binding.
the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s
Mutations in the increased-fidelity SpCas9 variants may reduce cleavage without reducing DNA binding.
the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s
Mutations in the increased-fidelity SpCas9 variants may reduce cleavage without reducing DNA binding.
the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s
Mutations in the increased-fidelity SpCas9 variants may reduce cleavage without reducing DNA binding.
the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s
Mutations in the increased-fidelity SpCas9 variants may reduce cleavage without reducing DNA binding.
the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s
Mutations in the increased-fidelity SpCas9 variants may reduce cleavage without reducing DNA binding.
the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s
Mutations in the increased-fidelity SpCas9 variants may reduce cleavage without reducing DNA binding.
the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s
Mutations in the increased-fidelity SpCas9 variants may reduce cleavage without reducing DNA binding.
the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s
Mutations in the increased-fidelity SpCas9 variants may reduce cleavage without reducing DNA binding.
the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s
Mutations in the increased-fidelity SpCas9 variants may reduce cleavage without reducing DNA binding.
the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s
Mutations in the increased-fidelity SpCas9 variants may reduce cleavage without reducing DNA binding.
the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s
Mutations in the increased-fidelity SpCas9 variants may reduce cleavage without reducing DNA binding.
the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s
Mutations in the increased-fidelity SpCas9 variants may reduce cleavage without reducing DNA binding.
the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s
Mutations in the increased-fidelity SpCas9 variants may reduce cleavage without reducing DNA binding.
the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s
Mutations in the increased-fidelity SpCas9 variants may reduce cleavage without reducing DNA binding.
the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s
Mutations in the increased-fidelity SpCas9 variants may reduce cleavage without reducing DNA binding.
the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s
Mutations in the increased-fidelity SpCas9 variants may reduce cleavage without reducing DNA binding.
the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s
The paper provides a framework for generating new nuclease variants for targets that currently lack a matching optimal nuclease and a simple means for identifying the optimal nuclease when accurate target-ranking prediction tools are absent.
We provide here a framework for generating new nuclease variants for targets that currently have no matching optimal nuclease, and offer a simple mean for identifying the optimal nuclease for targets in the absence of accurate target-ranking prediction tools
The paper provides a framework for generating new nuclease variants for targets that currently lack a matching optimal nuclease and a simple means for identifying the optimal nuclease when accurate target-ranking prediction tools are absent.
We provide here a framework for generating new nuclease variants for targets that currently have no matching optimal nuclease, and offer a simple mean for identifying the optimal nuclease for targets in the absence of accurate target-ranking prediction tools
The paper provides a framework for generating new nuclease variants for targets that currently lack a matching optimal nuclease and a simple means for identifying the optimal nuclease when accurate target-ranking prediction tools are absent.
We provide here a framework for generating new nuclease variants for targets that currently have no matching optimal nuclease, and offer a simple mean for identifying the optimal nuclease for targets in the absence of accurate target-ranking prediction tools
The paper provides a framework for generating new nuclease variants for targets that currently lack a matching optimal nuclease and a simple means for identifying the optimal nuclease when accurate target-ranking prediction tools are absent.
We provide here a framework for generating new nuclease variants for targets that currently have no matching optimal nuclease, and offer a simple mean for identifying the optimal nuclease for targets in the absence of accurate target-ranking prediction tools
The paper provides a framework for generating new nuclease variants for targets that currently lack a matching optimal nuclease and a simple means for identifying the optimal nuclease when accurate target-ranking prediction tools are absent.
We provide here a framework for generating new nuclease variants for targets that currently have no matching optimal nuclease, and offer a simple mean for identifying the optimal nuclease for targets in the absence of accurate target-ranking prediction tools
The paper provides a framework for generating new nuclease variants for targets that currently lack a matching optimal nuclease and a simple means for identifying the optimal nuclease when accurate target-ranking prediction tools are absent.
We provide here a framework for generating new nuclease variants for targets that currently have no matching optimal nuclease, and offer a simple mean for identifying the optimal nuclease for targets in the absence of accurate target-ranking prediction tools
The paper provides a framework for generating new nuclease variants for targets that currently lack a matching optimal nuclease and a simple means for identifying the optimal nuclease when accurate target-ranking prediction tools are absent.
We provide here a framework for generating new nuclease variants for targets that currently have no matching optimal nuclease, and offer a simple mean for identifying the optimal nuclease for targets in the absence of accurate target-ranking prediction tools
The paper provides a framework for generating new nuclease variants for targets that currently lack a matching optimal nuclease and a simple means for identifying the optimal nuclease when accurate target-ranking prediction tools are absent.
We provide here a framework for generating new nuclease variants for targets that currently have no matching optimal nuclease, and offer a simple mean for identifying the optimal nuclease for targets in the absence of accurate target-ranking prediction tools
The paper provides a framework for generating new nuclease variants for targets that currently lack a matching optimal nuclease and a simple means for identifying the optimal nuclease when accurate target-ranking prediction tools are absent.
We provide here a framework for generating new nuclease variants for targets that currently have no matching optimal nuclease, and offer a simple mean for identifying the optimal nuclease for targets in the absence of accurate target-ranking prediction tools
The paper provides a framework for generating new nuclease variants for targets that currently lack a matching optimal nuclease and a simple means for identifying the optimal nuclease when accurate target-ranking prediction tools are absent.
We provide here a framework for generating new nuclease variants for targets that currently have no matching optimal nuclease, and offer a simple mean for identifying the optimal nuclease for targets in the absence of accurate target-ranking prediction tools
The paper concerns crossing enhanced and high fidelity SpCas9 nucleases to optimize specificity and cleavage.
The paper concerns crossing enhanced and high fidelity SpCas9 nucleases to optimize specificity and cleavage.
The paper concerns crossing enhanced and high fidelity SpCas9 nucleases to optimize specificity and cleavage.
The paper concerns crossing enhanced and high fidelity SpCas9 nucleases to optimize specificity and cleavage.
The paper concerns crossing enhanced and high fidelity SpCas9 nucleases to optimize specificity and cleavage.
The paper concerns crossing enhanced and high fidelity SpCas9 nucleases to optimize specificity and cleavage.
The paper concerns crossing enhanced and high fidelity SpCas9 nucleases to optimize specificity and cleavage.
The paper concerns crossing enhanced and high fidelity SpCas9 nucleases to optimize specificity and cleavage.
The paper concerns crossing enhanced and high fidelity SpCas9 nucleases to optimize specificity and cleavage.
The paper concerns crossing enhanced and high fidelity SpCas9 nucleases to optimize specificity and cleavage.
HeFSpCas9 variants show substantially improved specificity for targets where eSpCas9 and SpCas9-HF1 have higher off-target propensity.
HeFSpCas9s exhibit substantially improved specificity specifically for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity
HeFSpCas9 variants show substantially improved specificity for targets where eSpCas9 and SpCas9-HF1 have higher off-target propensity.
HeFSpCas9s exhibit substantially improved specificity specifically for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity
HeFSpCas9 variants show substantially improved specificity for targets where eSpCas9 and SpCas9-HF1 have higher off-target propensity.
HeFSpCas9s exhibit substantially improved specificity specifically for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity
HeFSpCas9 variants show substantially improved specificity for targets where eSpCas9 and SpCas9-HF1 have higher off-target propensity.
HeFSpCas9s exhibit substantially improved specificity specifically for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity
HeFSpCas9 variants show substantially improved specificity for targets where eSpCas9 and SpCas9-HF1 have higher off-target propensity.
HeFSpCas9s exhibit substantially improved specificity specifically for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity
HeFSpCas9 variants show substantially improved specificity for targets where eSpCas9 and SpCas9-HF1 have higher off-target propensity.
HeFSpCas9s exhibit substantially improved specificity specifically for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity
HeFSpCas9 variants show substantially improved specificity for targets where eSpCas9 and SpCas9-HF1 have higher off-target propensity.
HeFSpCas9s exhibit substantially improved specificity specifically for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity
HeFSpCas9 variants show substantially improved specificity for targets where eSpCas9 and SpCas9-HF1 have higher off-target propensity.
HeFSpCas9s exhibit substantially improved specificity specifically for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity
HeFSpCas9 variants show substantially improved specificity for targets where eSpCas9 and SpCas9-HF1 have higher off-target propensity.
HeFSpCas9s exhibit substantially improved specificity specifically for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity
HeFSpCas9 variants show substantially improved specificity for targets where eSpCas9 and SpCas9-HF1 have higher off-target propensity.
HeFSpCas9s exhibit substantially improved specificity specifically for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity
HeFSpCas9 variants show substantially improved specificity for targets where eSpCas9 and SpCas9-HF1 have higher off-target propensity.
HeFSpCas9s exhibit substantially improved specificity specifically for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity
HeFSpCas9 variants show substantially improved specificity for targets where eSpCas9 and SpCas9-HF1 have higher off-target propensity.
HeFSpCas9s exhibit substantially improved specificity specifically for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity
HeFSpCas9 variants show substantially improved specificity for targets where eSpCas9 and SpCas9-HF1 have higher off-target propensity.
HeFSpCas9s exhibit substantially improved specificity specifically for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity
HeFSpCas9 variants show substantially improved specificity for targets where eSpCas9 and SpCas9-HF1 have higher off-target propensity.
HeFSpCas9s exhibit substantially improved specificity specifically for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity
HeFSpCas9 variants show substantially improved specificity for targets where eSpCas9 and SpCas9-HF1 have higher off-target propensity.
HeFSpCas9s exhibit substantially improved specificity specifically for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity
HeFSpCas9 variants show substantially improved specificity for targets where eSpCas9 and SpCas9-HF1 have higher off-target propensity.
HeFSpCas9s exhibit substantially improved specificity specifically for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity
HeFSpCas9 variants show substantially improved specificity for targets where eSpCas9 and SpCas9-HF1 have higher off-target propensity.
HeFSpCas9s exhibit substantially improved specificity specifically for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity
Targets can be ranked by cleavability and off-target effects as manifested by the increased-fidelity nucleases.
There is also a ranking among the targets by their cleavability and off-target effects manifested by the increased fidelity nucleases
Targets can be ranked by cleavability and off-target effects as manifested by the increased-fidelity nucleases.
There is also a ranking among the targets by their cleavability and off-target effects manifested by the increased fidelity nucleases
Targets can be ranked by cleavability and off-target effects as manifested by the increased-fidelity nucleases.
There is also a ranking among the targets by their cleavability and off-target effects manifested by the increased fidelity nucleases
Targets can be ranked by cleavability and off-target effects as manifested by the increased-fidelity nucleases.
There is also a ranking among the targets by their cleavability and off-target effects manifested by the increased fidelity nucleases
Targets can be ranked by cleavability and off-target effects as manifested by the increased-fidelity nucleases.
There is also a ranking among the targets by their cleavability and off-target effects manifested by the increased fidelity nucleases
Targets can be ranked by cleavability and off-target effects as manifested by the increased-fidelity nucleases.
There is also a ranking among the targets by their cleavability and off-target effects manifested by the increased fidelity nucleases
Targets can be ranked by cleavability and off-target effects as manifested by the increased-fidelity nucleases.
There is also a ranking among the targets by their cleavability and off-target effects manifested by the increased fidelity nucleases
Targets can be ranked by cleavability and off-target effects as manifested by the increased-fidelity nucleases.
There is also a ranking among the targets by their cleavability and off-target effects manifested by the increased fidelity nucleases
Targets can be ranked by cleavability and off-target effects as manifested by the increased-fidelity nucleases.
There is also a ranking among the targets by their cleavability and off-target effects manifested by the increased fidelity nucleases
Targets can be ranked by cleavability and off-target effects as manifested by the increased-fidelity nucleases.
There is also a ranking among the targets by their cleavability and off-target effects manifested by the increased fidelity nucleases
Targets can be ranked by cleavability and off-target effects as manifested by the increased-fidelity nucleases.
There is also a ranking among the targets by their cleavability and off-target effects manifested by the increased fidelity nucleases
Targets can be ranked by cleavability and off-target effects as manifested by the increased-fidelity nucleases.
There is also a ranking among the targets by their cleavability and off-target effects manifested by the increased fidelity nucleases
Targets can be ranked by cleavability and off-target effects as manifested by the increased-fidelity nucleases.
There is also a ranking among the targets by their cleavability and off-target effects manifested by the increased fidelity nucleases
Targets can be ranked by cleavability and off-target effects as manifested by the increased-fidelity nucleases.
There is also a ranking among the targets by their cleavability and off-target effects manifested by the increased fidelity nucleases
Targets can be ranked by cleavability and off-target effects as manifested by the increased-fidelity nucleases.
There is also a ranking among the targets by their cleavability and off-target effects manifested by the increased fidelity nucleases
Targets can be ranked by cleavability and off-target effects as manifested by the increased-fidelity nucleases.
There is also a ranking among the targets by their cleavability and off-target effects manifested by the increased fidelity nucleases
Targets can be ranked by cleavability and off-target effects as manifested by the increased-fidelity nucleases.
There is also a ranking among the targets by their cleavability and off-target effects manifested by the increased fidelity nucleases
The three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers.
These three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers
The three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers.
These three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers
The three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers.
These three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers
The three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers.
These three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers
The three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers.
These three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers
The three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers.
These three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers
The three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers.
These three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers
The three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers.
These three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers
The three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers.
These three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers
The three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers.
These three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers
The three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers.
These three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers
The three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers.
These three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers
The three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers.
These three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers
The three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers.
These three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers
The three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers.
These three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers
The three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers.
These three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers
The three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers.
These three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers
Approval Evidence
1 source8 linked approval claimsfirst-pass slug spcas9-hf1
SpCas9-HF1
Source:
activity effectsupports
For the increased-fidelity nucleases, a matching 5' G extension is more detrimental to activity than a mismatching 5' G extension.
a matching 5' G extension being more detrimental to their activities than a mismatching one
Source:
application guidancesupports
For highest-specificity cleavage, each target should be matched with an appropriate high-fidelity nuclease.
for highest specificity cleavage, each target needs to be matched with an appropriate high fidelity nuclease
Source:
comparative conclusionsupports
No single high-fidelity SpCas9 nuclease variant is generally superior in fidelity across targets.
No single nuclease variant shows generally superior fidelity
Source:
engineering resultsupports
HeFSpCas9 variants were generated by combining mutations from eSpCas9 and SpCas9-HF1.
we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1
Source:
mechanistic effectsupports
Mutations in the increased-fidelity SpCas9 variants may reduce cleavage without reducing DNA binding.
the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s
Source:
specificity improvementsupports
HeFSpCas9 variants show substantially improved specificity for targets where eSpCas9 and SpCas9-HF1 have higher off-target propensity.
HeFSpCas9s exhibit substantially improved specificity specifically for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity
Source:
target dependencesupports
Targets can be ranked by cleavability and off-target effects as manifested by the increased-fidelity nucleases.
There is also a ranking among the targets by their cleavability and off-target effects manifested by the increased fidelity nucleases
Source:
usage constraintsupports
The three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers.
These three increased-fidelity nucleases can routinely be used only with perfectly matching 20 nucleotide-long spacers
Source:
Comparisons
Source-backed strengths
The available evidence places SpCas9-HF1 among increased-fidelity nucleases specifically compared for cleavage specificity optimization across targets. The study further reports a guide-design-related activity effect in this class, namely that a matching 5' G extension is more detrimental to activity than a mismatching 5' G extension.
Source:
No single nuclease variant shows generally superior fidelity
Source:
we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1
Source:
The paper concerns crossing enhanced and high fidelity SpCas9 nucleases to optimize specificity and cleavage.
Compared with eSpCas9
SpCas9-HF1 and eSpCas9 address a similar problem space because they share recombination.
Shared frame: same top-level item type; shared target processes: recombination; shared mechanisms: dna binding, dna cleavage, dna_binding, photocleavage
Compared with LHCII N-terminal domain
SpCas9-HF1 and LHCII N-terminal domain address a similar problem space because they share recombination.
Shared frame: same top-level item type; shared target processes: recombination; shared mechanisms: photocleavage
Strengths here: looks easier to implement in practice.
Compared with SpCas9
SpCas9-HF1 and SpCas9 address a similar problem space because they share recombination.
Shared frame: same top-level item type; shared target processes: recombination; shared mechanisms: dna binding, dna_binding, photocleavage
Relative tradeoffs: appears more independently replicated; looks easier to implement in practice.
Ranked Citations
- 1.