Source 1review2021Frontiers in Genome Editing
Toolkit/ex vivo gene editing with programmable nucleases
ex vivo gene editing with programmable nucleases
Taxonomy: Technique Branch / Method. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Ex vivo gene editing with programmable nucleases is an engineering approach for site-specific genome modification in human hematopoietic stem and progenitor cells (HSPCs). The cited literature describes it as a state-of-the-art strategy that extends gene therapy beyond semi-random gene addition.
Usefulness & Problems
Why this is useful
This approach is useful because programmable nucleases such as CRISPR/Cas9 enable site-specific genome modification in HSPCs rather than semi-random gene addition. The cited review further presents site-specific modification as promising for safer genetic manipulation.
Source:
With the advent of novel programmable nucleases, such as CRISPR/Cas9, it has been possible to expand the applications of gene therapy beyond semi-random gene addition to site-specific modification of the genome
Problem solved
It addresses the limitation of earlier gene therapy strategies based on semi-random gene addition by enabling targeted genome modification. In the supplied evidence, this problem is framed specifically in the context of ex vivo editing of human HSPCs.
Problem links
Need controllable genome or transcript editing
DerivedEx vivo gene editing with programmable nucleases is an engineering approach for site-specific genome modification in human hematopoietic stem and progenitor cells (HSPCs). The cited literature describes it as a state-of-the-art strategy that extends gene therapy beyond semi-random gene addition.
Need tighter control over protein production
DerivedEx vivo gene editing with programmable nucleases is an engineering approach for site-specific genome modification in human hematopoietic stem and progenitor cells (HSPCs). The cited literature describes it as a state-of-the-art strategy that extends gene therapy beyond semi-random gene addition.
Taxonomy & Function
Primary hierarchy
Technique Branch
Method: A concrete method used to build, optimize, or evolve an engineered system.
Techniques
No technique tags yet.
Target processes
editingtranslationImplementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationoperating role: builder
The evidence specifies an ex vivo workflow in human hematopoietic stem and progenitor cells. No further practical details are provided in the supplied material regarding nuclease format, delivery method, culture conditions, donor templates, or construct design.
The supplied evidence does not provide quantitative performance data, editing efficiencies, target loci, or comparative outcomes across nuclease platforms. It also does not document independent replication, clinical efficacy, or specific safety liabilities beyond a general promise of safer manipulation.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
Programmable nucleases such as CRISPR/Cas9 expanded gene therapy applications from semi-random gene addition to site-specific genome modification.
With the advent of novel programmable nucleases, such as CRISPR/Cas9, it has been possible to expand the applications of gene therapy beyond semi-random gene addition to site-specific modification of the genome
Site-specific genome modification is presented as holding promise for safer genetic manipulation.
site-specific modification of the genome, holding the promise for safer genetic manipulation
Site-specific genome modification is presented as holding promise for safer genetic manipulation.
site-specific modification of the genome, holding the promise for safer genetic manipulation
Site-specific genome modification is presented as holding promise for safer genetic manipulation.
site-specific modification of the genome, holding the promise for safer genetic manipulation
Site-specific genome modification is presented as holding promise for safer genetic manipulation.
site-specific modification of the genome, holding the promise for safer genetic manipulation
Site-specific genome modification is presented as holding promise for safer genetic manipulation.
site-specific modification of the genome, holding the promise for safer genetic manipulation
Site-specific genome modification is presented as holding promise for safer genetic manipulation.
site-specific modification of the genome, holding the promise for safer genetic manipulation
Site-specific genome modification is presented as holding promise for safer genetic manipulation.
site-specific modification of the genome, holding the promise for safer genetic manipulation
Clinical translation of gene editing in human HSPCs faces current challenges despite potential advantages.
We highlight the potential advantages and the current challenges toward safe and effective clinical translation of gene editing for the treatment of hematological diseases.
Clinical translation of gene editing in human HSPCs faces current challenges despite potential advantages.
We highlight the potential advantages and the current challenges toward safe and effective clinical translation of gene editing for the treatment of hematological diseases.
Clinical translation of gene editing in human HSPCs faces current challenges despite potential advantages.
We highlight the potential advantages and the current challenges toward safe and effective clinical translation of gene editing for the treatment of hematological diseases.
Clinical translation of gene editing in human HSPCs faces current challenges despite potential advantages.
We highlight the potential advantages and the current challenges toward safe and effective clinical translation of gene editing for the treatment of hematological diseases.
Clinical translation of gene editing in human HSPCs faces current challenges despite potential advantages.
We highlight the potential advantages and the current challenges toward safe and effective clinical translation of gene editing for the treatment of hematological diseases.
Clinical translation of gene editing in human HSPCs faces current challenges despite potential advantages.
We highlight the potential advantages and the current challenges toward safe and effective clinical translation of gene editing for the treatment of hematological diseases.
Clinical translation of gene editing in human HSPCs faces current challenges despite potential advantages.
We highlight the potential advantages and the current challenges toward safe and effective clinical translation of gene editing for the treatment of hematological diseases.
Approval Evidence
1 source2 linked approval claimsfirst-pass slug ex-vivo-gene-editing-with-programmable-nucleases
Here we review the state of the art of ex vivo gene editing with programmable nucleases in human hematopoietic stem and progenitor cells (HSPCs).
Source:
safety promisesupports
Site-specific genome modification is presented as holding promise for safer genetic manipulation.
site-specific modification of the genome, holding the promise for safer genetic manipulation
Source:
translation challengemixed
Clinical translation of gene editing in human HSPCs faces current challenges despite potential advantages.
We highlight the potential advantages and the current challenges toward safe and effective clinical translation of gene editing for the treatment of hematological diseases.
Source:
Comparisons
Source-backed strengths
The main strength supported by the evidence is the ability to perform site-specific genome modification using programmable nucleases, including CRISPR/Cas9. The literature also characterizes this ex vivo HSPC editing paradigm as state of the art and as holding promise for safer genetic manipulation.
Compared with base editing
ex vivo gene editing with programmable nucleases and base editing address a similar problem space because they share editing, translation.
Shared frame: same top-level item type; shared target processes: editing, translation; shared mechanisms: translation_control
Strengths here: looks easier to implement in practice; may avoid an exogenous cofactor requirement.
Relative tradeoffs: appears more independently replicated.
Compared with haplotype-by-epigenotype prediction
ex vivo gene editing with programmable nucleases and haplotype-by-epigenotype prediction address a similar problem space because they share editing, translation.
Shared frame: same top-level item type; shared target processes: editing, translation; shared mechanisms: translation_control
Compared with proximity labeling
ex vivo gene editing with programmable nucleases and proximity labeling address a similar problem space because they share editing, translation.
Shared frame: same top-level item type; shared target processes: editing, translation; shared mechanisms: translation_control
Ranked Citations
- 1.