Toolkit/compact PE

compact PE

Multi-Component Switch·Research·Since 2021

Also known as: compact PE2, truncated reverse transcriptase prime editor

Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.

Summary

Compact PE is a truncated prime editor in which the reverse transcriptase RNase H domain is completely deleted. In the cited 2021 study, this compact PE showed editing activity comparable to full-length PE2 and enabled flexible split prime editor designs for in vivo delivery.

Usefulness & Problems

Why this is useful

This tool is useful because it reduces prime editor size while preserving editing performance in the reported study. The same study positions this size reduction as enabling more flexible split prime editor architectures for efficient in vivo delivery and improving safety by abolishing eRF1 binding with minimal effect on stop codon readthrough.

Source:

This study identifies a safe and efficient compact PE2 that enables flexible split-PE design to facilitate efficient delivery in vivo

Problem solved

Compact PE addresses the engineering problem that full-length prime editors are large and less amenable to flexible split designs for in vivo delivery. It also addresses a safety-related concern by removing the reverse transcriptase RNase H domain associated in the study with eRF1 binding and 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.

Target processes

editing

Implementation Constraints

The defining construct feature is complete deletion of the reverse transcriptase RNase H domain from PE2. The study indicates compatibility with split prime editor design for in vivo delivery, but the supplied evidence does not provide construct junctions, split sites, expression systems, or vector specifications.

The evidence provided comes from a single 2021 source and does not specify editing contexts, target range, cell types, or quantitative performance metrics in this summary. No independent replication, delivery vehicle details, or long-term in vivo validation are described in the supplied evidence.

Validation

Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication

Supporting Sources

Ranked Claims

Claim 1application potentialsupports2021Source 1needs review

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
Claim 2application potentialsupports2021Source 1needs review

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
Claim 3application potentialsupports2021Source 1needs review

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
Claim 4application potentialsupports2021Source 1needs review

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
Claim 5application potentialsupports2021Source 1needs review

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
Claim 6application potentialsupports2021Source 1needs review

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
Claim 7application potentialsupports2021Source 1needs review

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
Claim 8engineering resultsupports2021Source 1needs review

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
Claim 9engineering resultsupports2021Source 1needs review

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
Claim 10engineering resultsupports2021Source 1needs review

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
Claim 11engineering resultsupports2021Source 1needs review

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
Claim 12engineering resultsupports2021Source 1needs review

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
Claim 13engineering resultsupports2021Source 1needs review

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
Claim 14engineering resultsupports2021Source 1needs review

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
Claim 15mechanistic safetysupports2021Source 1needs review

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
Claim 16mechanistic safetysupports2021Source 1needs review

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
Claim 17mechanistic safetysupports2021Source 1needs review

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
Claim 18mechanistic safetysupports2021Source 1needs review

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
Claim 19mechanistic safetysupports2021Source 1needs review

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
Claim 20mechanistic safetysupports2021Source 1needs review

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
Claim 21mechanistic safetysupports2021Source 1needs review

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
Claim 22performance comparisonsupports2021Source 1needs review

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 %
Claim 23performance comparisonsupports2021Source 1needs review

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 %
Claim 24performance comparisonsupports2021Source 1needs review

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 %
Claim 25performance comparisonsupports2021Source 1needs review

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 %
Claim 26performance comparisonsupports2021Source 1needs review

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 %
Claim 27performance comparisonsupports2021Source 1needs review

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 %
Claim 28performance comparisonsupports2021Source 1needs review

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 source4 linked approval claimsfirst-pass slug compact-pe
Here, we developed a compact PE with complete deletion of the RNase H domain of reverse transcriptase (RT)

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:

engineering resultsupports

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

Source:

mechanistic safetysupports

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

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

The reported compact PE retained editing activity comparable to full-length PE2 despite complete deletion of the reverse transcriptase RNase H domain. The study further reports abolished eRF1 binding, minimal effect on stop codon readthrough, and utility for flexible split prime editor design aimed at efficient in vivo delivery.

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. 1.

    Extracted from this source document.