Gap in Seattle Hub lineage tracing: In-vivo Prime Editing for Recording and Repair

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Composite

82%

Novelty

83%

Mechanistic

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Druggability

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Priority

82%

Importance

80%

Tractability

80%

Market price

50%

Description

Determine which delivery and pegRNA designs make in-vivo prime editing efficient enough for cell recording or therapeutic repair. Boundary domains: gene-therapy, delivery-systems. Representative papers: Engineered virus-like particles for efficient in vivo delivery of therapeutic proteins.; In vivo base editing rescues Hutchinson-Gilford progeria syndrome in mice.; Efficient in vivo genome editing prevents hypertrophic cardiomyopathy in mice.

Resolution criteria

Resolution requires: (1) In vivo prime editing efficiency >=15% with <=5% off-target edits; (2) pegRNA design algorithm improving efficiency >=2-fold over random; (3) Therapeutic editing demonstrated in >=1 disease model; (4) Delivery validated for prime editor cargo (>=8kb). Deliverable: optimized pegRNA design tool + therapeutic proof-of-concept.

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