Bounded definition
The 2019 founding study demonstrated targeted substitutions, insertions, and deletions using prime editors in four human cell lines and primary post-mitotic mouse cortical neurons, with efficiency varying by edit and system. Within this page, that proposition is limited to The experiments, cell systems, loci, editor variants, assays, and comparisons reported in the founding Nature paper and its supplementary information.
Definition and evidence boundary
A genome-editing method coupling a Cas9 nickase–reverse-transcriptase fusion with a prime-editing guide RNA that identifies a target and encodes a desired edit. The bounded proposition retained by the canonical record is: The 2019 founding study demonstrated targeted substitutions, insertions, and deletions using prime editors in four human cell lines and primary post-mitotic mouse cortical neurons, with efficiency varying by edit and system.
The applicable scope is The experiments, cell systems, loci, editor variants, assays, and comparisons reported in the founding Nature paper and its supplementary information. This definition must not be generalized beyond the cited source and exact record boundary.
Claims: urn:maha:claim:prime-editing-demonstration
Mechanism and technical context
The paper introduces the prime-editing architecture and reports targeted edit classes across specified human cell lines and primary mouse neurons with experiment-dependent efficiencies and byproducts. This is the source-bound technical context for the record; no uncited mechanism is added by the compiler.
The experiments do not establish safe delivery, whole-organism efficacy, long-term clinical outcomes, or suitability for any individual treatment. The mechanism or method is therefore presented as one component of a larger system, not as evidence for every downstream outcome.
Claims: urn:maha:claim:prime-editing-demonstration
How to interpret the evidence
The source reports experiment-specific means and variation; there is no single valid efficiency or error interval for prime editing across targets and biological systems. The evidence maturity recorded here is single study, and the claim kind is empirical claim.
This Phase 1 record is deliberately bounded to the founding study and does not yet compile independent replication evidence. It is not clinical evidence, does not establish delivery to human tissues, and does not provide a universal safety or efficacy estimate for all prime-editor designs. These qualifications travel with the claim whenever it is reused.
Claims: urn:maha:claim:prime-editing-demonstration
What the source supports and what remains unknown
The inspected source supports exactly this: The paper introduces the prime-editing architecture and reports targeted edit classes across specified human cell lines and primary mouse neurons with experiment-dependent efficiencies and byproducts. It was read at Abstract; Figures 1–5; Methods; Extended Data; Supplementary Tables 1–5.
What remains unknown is everything outside that locator. The experiments do not establish safe delivery, whole-organism efficacy, long-term clinical outcomes, or suitability for any individual treatment. No quantity, comparison, or downstream outcome is established here unless a separately scoped record measures it.
Claims: urn:maha:claim:prime-editing-demonstration
Source identity, locator, and reuse boundary
The bound source is “Search-and-replace genome editing without double-strand breaks or donor DNA” by Andrew V. Anzalone, Peyton B. Randolph, Jessie R. Davis, Alexander A. Sousa, Luke W. Koblan, et al., published by Nature on 2019-10-21; its declared stable identity is doi:10.1038/s41586-019-1711-4, accession:PRJNA565979.
The inspected-content locator is Abstract; Figures 1–5; Methods; Extended Data; Supplementary Tables 1–5. Reuse is limited to citation-with-paraphrase. The Maha page paraphrases the reported method and scope, links to the version of record, and reproduces no paywalled passage. This metadata establishes source identity and inspection scope, not the truth of claims outside the cited locator.
Claims: urn:maha:claim:prime-editing-demonstration
Comparison and calculation boundary
Applicability is decided explicitly, not filled with generic material.
This record carries 1 source-bound proposition and therefore has no second supported side. A comparison would have to be manufactured from an adjacent title rather than from a second inspected claim, which the gate forbids.
The canonical claim declares no reproducible numerical inputs, equation, units, or uncertainty propagation; recorded uncertainty kind is quantitative. Supplying sample values would invent an unsupported quantitative result.
Limitations and prohibited inference
The claim stops where its evidence stops.
- record boundary
In-vitro or ex-vivo editing performance does not establish in-vivo delivery, safety, efficacy, or clinical benefit.
- record boundary
Efficiency and byproduct measurements are target-, editor-, protocol-, assay-, and cell-system-specific.
- prohibited inference
Do not use this record as medical advice or as evidence that a disease can currently be treated safely with prime editing.
- prohibited inference
Do not generalize one experiment’s efficiency or off-target result to all prime editors, targets, tissues, or delivery systems.
- editorial
This compilation reorganizes an existing inspected claim and its declared source; it does not add a new experiment, measurement, or independent replication.
- editorial
Internal editorial inspection is not external peer review, and no result on this page has been independently reproduced.
Related records and mathematical bridges
Typed links expose context without asserting equivalence.
Adenine base editing
Same canonical domain (synthetic-biology). Domain membership only: no shared source or declared edge links these two records.
Selection: domain adjacency
Editing efficiency and byproduct measurement
Declared mechanistic-dependency edge into this record, so it is positioned earlier in the same bounded sequence.
Selection: bridge edge
Prime-editing guide RNA mechanism
Declared mechanistic-dependency edge into this record, so it is positioned earlier in the same bounded sequence.
Selection: bridge edge
When no declared bridge edge is present, related records are linked by shared evidence or canonical domain adjacency. Those links are navigational and do not claim mathematical or physical equivalence.
Connected domain graph
Typed dependencies preserve publication state.
Only independently canonical records receive public links and relation statements. Draft graph topology remains private.
Prime-editing guide RNA mechanism
inbound connection · mechanism
The pegRNA and fused editor form the central mechanism of the prime-editing method.
Editing efficiency and byproduct measurement
inbound connection · measurement
Prime-editing performance is an empirical distribution of products, not one method-wide percentage.
Claim ledger
Every proposition keeps its own evidence state.
The 2019 founding study demonstrated targeted substitutions, insertions, and deletions using prime editors in four human cell lines and primary post-mitotic mouse cortical neurons, with efficiency varying by edit and system.
- Scope
- The experiments, cell systems, loci, editor variants, assays, and comparisons reported in the founding Nature paper and its supplementary information.
- Boundary
- The experiments do not establish safe delivery, whole-organism efficacy, long-term clinical outcomes, or suitability for any individual treatment.
- Uncertainty
- The source reports experiment-specific means and variation; there is no single valid efficiency or error interval for prime editing across targets and biological systems.
- Replication
- This Phase 1 record is deliberately bounded to the founding study and does not yet compile independent replication evidence.
Primary sources
Citation, locator, rights, and boundary travel together.
Source 1 · Nature
Search-and-replace genome editing without double-strand breaks or donor DNA
Andrew V. Anzalone, Peyton B. Randolph, Jessie R. Davis, Alexander A. Sousa, Luke W. Koblan, et al.
- Exact locator
- Abstract; Figures 1–5; Methods; Extended Data; Supplementary Tables 1–5.
- Establishes
- The paper introduces the prime-editing architecture and reports targeted edit classes across specified human cell lines and primary mouse neurons with experiment-dependent efficiencies and byproducts.
- Boundary
- It is not clinical evidence, does not establish delivery to human tissues, and does not provide a universal safety or efficacy estimate for all prime-editor designs.
- Rights basis
- citation with paraphrase · The Maha page paraphrases the reported method and scope, links to the version of record, and reproduces no paywalled passage.
- Declared interests
- The publisher record states that authors filed patent applications and identifies company relationships involving genome-editing technologies.