Source 1primary paper2021
Toolkit/split prime editor
split prime editor
Also known as: split-PE
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Split prime editor is a multi-component prime editing system in which prime editor is divided into two fragments to support flexible split configurations and dual-adeno-associated virus delivery. The reported design was enabled by a compact PE2 variant with complete deletion of the reverse transcriptase RNase H domain while retaining editing activity comparable to full-length prime editor.
Usefulness & Problems
Why this is useful
This tool is useful for in vivo deployment of prime editing when cargo size constrains delivery, because splitting the editor into two fragments can facilitate dual-AAV packaging. The compact PE2 design also reduced eRF1 interaction and showed minimal effect on stop codon readthrough, supporting a potentially safer editor architecture.
Source:
This study identifies a safe and efficient compact PE2 that enables flexible split-PE design to facilitate efficient delivery in vivo
Problem solved
It addresses the delivery challenge posed by the large size of prime editors, which can limit packaging into adeno-associated virus vectors. It also addresses a safety-related concern by using an RNase H-deleted reverse transcriptase variant that abolished detectable eRF1 binding and minimized stop codon readthrough effects.
Source:
This study identifies a safe and efficient compact PE2 that enables flexible split-PE design to facilitate efficient delivery in vivo
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.
Techniques
Computational DesignTarget processes
editingImplementation Constraints
The reported implementation uses a split prime editor architecture in which prime editor is divided into two fragments for dual-AAV delivery. A key construct design feature is complete deletion of the reverse transcriptase RNase H domain to generate a compact PE2 variant; the provided evidence does not specify split junctions, linker designs, or expression context.
The supplied evidence is limited to a single 2021 study and does not provide detailed quantitative editing efficiencies, target scope, or organism-specific validation in this summary. Independent replication, long-term in vivo performance, and practical details of fragment reconstitution are not documented in the provided evidence.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
The study identifies a safe and efficient compact PE2 that enables flexible split prime editor design to facilitate efficient in vivo delivery.
This study identifies a safe and efficient compact PE2 that enables flexible split-PE design to facilitate efficient delivery in vivo
The study identifies a safe and efficient compact PE2 that enables flexible split prime editor design to facilitate efficient in vivo delivery.
This study identifies a safe and efficient compact PE2 that enables flexible split-PE design to facilitate efficient delivery in vivo
The study identifies a safe and efficient compact PE2 that enables flexible split prime editor design to facilitate efficient in vivo delivery.
This study identifies a safe and efficient compact PE2 that enables flexible split-PE design to facilitate efficient delivery in vivo
The study identifies a safe and efficient compact PE2 that enables flexible split prime editor design to facilitate efficient in vivo delivery.
This study identifies a safe and efficient compact PE2 that enables flexible split-PE design to facilitate efficient delivery in vivo
The study identifies a safe and efficient compact PE2 that enables flexible split prime editor design to facilitate efficient in vivo delivery.
This study identifies a safe and efficient compact PE2 that enables flexible split-PE design to facilitate efficient delivery in vivo
The study identifies a safe and efficient compact PE2 that enables flexible split prime editor design to facilitate efficient in vivo delivery.
This study identifies a safe and efficient compact PE2 that enables flexible split-PE design to facilitate efficient delivery in vivo
The study identifies a safe and efficient compact PE2 that enables flexible split prime editor design to facilitate efficient in vivo delivery.
This study identifies a safe and efficient compact PE2 that enables flexible split-PE design to facilitate efficient delivery in vivo
A compact prime editor with complete deletion of the reverse transcriptase RNase H domain showed comparable editing to full-length prime editor.
we developed a compact PE with complete deletion of the RNase H domain of reverse transcriptase (RT), which showed comparable editing to full-length PE
A compact prime editor with complete deletion of the reverse transcriptase RNase H domain showed comparable editing to full-length prime editor.
we developed a compact PE with complete deletion of the RNase H domain of reverse transcriptase (RT), which showed comparable editing to full-length PE
A compact prime editor with complete deletion of the reverse transcriptase RNase H domain showed comparable editing to full-length prime editor.
we developed a compact PE with complete deletion of the RNase H domain of reverse transcriptase (RT), which showed comparable editing to full-length PE
A compact prime editor with complete deletion of the reverse transcriptase RNase H domain showed comparable editing to full-length prime editor.
we developed a compact PE with complete deletion of the RNase H domain of reverse transcriptase (RT), which showed comparable editing to full-length PE
A compact prime editor with complete deletion of the reverse transcriptase RNase H domain showed comparable editing to full-length prime editor.
we developed a compact PE with complete deletion of the RNase H domain of reverse transcriptase (RT), which showed comparable editing to full-length PE
A compact prime editor with complete deletion of the reverse transcriptase RNase H domain showed comparable editing to full-length prime editor.
we developed a compact PE with complete deletion of the RNase H domain of reverse transcriptase (RT), which showed comparable editing to full-length PE
A compact prime editor with complete deletion of the reverse transcriptase RNase H domain showed comparable editing to full-length prime editor.
we developed a compact PE with complete deletion of the RNase H domain of reverse transcriptase (RT), which showed comparable editing to full-length PE
The compact prime editor, unlike PE2, abolished binding to eRF1 and had minimal effect on stop codon readthrough.
The compact PE, but not PE2, abolished its binding to eRF1 and showed minimal effect on stop codon readthrough
The compact prime editor, unlike PE2, abolished binding to eRF1 and had minimal effect on stop codon readthrough.
The compact PE, but not PE2, abolished its binding to eRF1 and showed minimal effect on stop codon readthrough
The compact prime editor, unlike PE2, abolished binding to eRF1 and had minimal effect on stop codon readthrough.
The compact PE, but not PE2, abolished its binding to eRF1 and showed minimal effect on stop codon readthrough
The compact prime editor, unlike PE2, abolished binding to eRF1 and had minimal effect on stop codon readthrough.
The compact PE, but not PE2, abolished its binding to eRF1 and showed minimal effect on stop codon readthrough
The compact prime editor, unlike PE2, abolished binding to eRF1 and had minimal effect on stop codon readthrough.
The compact PE, but not PE2, abolished its binding to eRF1 and showed minimal effect on stop codon readthrough
The compact prime editor, unlike PE2, abolished binding to eRF1 and had minimal effect on stop codon readthrough.
The compact PE, but not PE2, abolished its binding to eRF1 and showed minimal effect on stop codon readthrough
The compact prime editor, unlike PE2, abolished binding to eRF1 and had minimal effect on stop codon readthrough.
The compact PE, but not PE2, abolished its binding to eRF1 and showed minimal effect on stop codon readthrough
Using the compact prime editor, the Cas9 Glu573 split site supported robust editing up to 93% of full-length prime editor.
Using compact PE, we tested the effect of 4 different Cas9 split sites and found that the Glu 573 split site supports robust editing (up to 93% of full-length PE)
editing relative to full-length PE 93 %
Using the compact prime editor, the Cas9 Glu573 split site supported robust editing up to 93% of full-length prime editor.
Using compact PE, we tested the effect of 4 different Cas9 split sites and found that the Glu 573 split site supports robust editing (up to 93% of full-length PE)
editing relative to full-length PE 93 %
Using the compact prime editor, the Cas9 Glu573 split site supported robust editing up to 93% of full-length prime editor.
Using compact PE, we tested the effect of 4 different Cas9 split sites and found that the Glu 573 split site supports robust editing (up to 93% of full-length PE)
editing relative to full-length PE 93 %
Using the compact prime editor, the Cas9 Glu573 split site supported robust editing up to 93% of full-length prime editor.
Using compact PE, we tested the effect of 4 different Cas9 split sites and found that the Glu 573 split site supports robust editing (up to 93% of full-length PE)
editing relative to full-length PE 93 %
Using the compact prime editor, the Cas9 Glu573 split site supported robust editing up to 93% of full-length prime editor.
Using compact PE, we tested the effect of 4 different Cas9 split sites and found that the Glu 573 split site supports robust editing (up to 93% of full-length PE)
editing relative to full-length PE 93 %
Using the compact prime editor, the Cas9 Glu573 split site supported robust editing up to 93% of full-length prime editor.
Using compact PE, we tested the effect of 4 different Cas9 split sites and found that the Glu 573 split site supports robust editing (up to 93% of full-length PE)
editing relative to full-length PE 93 %
Using the compact prime editor, the Cas9 Glu573 split site supported robust editing up to 93% of full-length prime editor.
Using compact PE, we tested the effect of 4 different Cas9 split sites and found that the Glu 573 split site supports robust editing (up to 93% of full-length PE)
editing relative to full-length PE 93 %
Approval Evidence
1 source2 linked approval claimsfirst-pass slug split-prime-editor
Although PE can be split into two fragments and delivered using dual adeno-associated viruses (AAVs)
Source:
application potentialsupports
The study identifies a safe and efficient compact PE2 that enables flexible split prime editor design to facilitate efficient in vivo delivery.
This study identifies a safe and efficient compact PE2 that enables flexible split-PE design to facilitate efficient delivery in vivo
Source:
performance comparisonsupports
Using the compact prime editor, the Cas9 Glu573 split site supported robust editing up to 93% of full-length prime editor.
Using compact PE, we tested the effect of 4 different Cas9 split sites and found that the Glu 573 split site supports robust editing (up to 93% of full-length PE)
Source:
Comparisons
Source-backed strengths
A compact prime editor with complete deletion of the reverse transcriptase RNase H domain showed comparable editing to full-length prime editor in the cited study. The study further states that this compact PE2 enabled flexible split prime editor design for efficient in vivo delivery and abolished binding to eRF1 with minimal effect on stop codon readthrough.
Source:
we developed a compact PE with complete deletion of the RNase H domain of reverse transcriptase (RT), which showed comparable editing to full-length PE
Source:
Using compact PE, we tested the effect of 4 different Cas9 split sites and found that the Glu 573 split site supports robust editing (up to 93% of full-length PE)
Ranked Citations
- 1.