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US 12,753,397 B2Granted
Prime editor system for in vivo genome editing
AssigneeUniversity of Massachusetts
InventorsShun-Qing Liang, Pengpeng Liu, Wen Xue, Scot Wolfe
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Abstract
The present applications discloses an NLS-optimized SpCas9-based prime editor that improves genome editing efficiency exemplified by endogenous loci in cultured cell lines. Using this genome modification system, tumor formation can be initiated through somatic cell editing in the adult mouse. Furthermore, a dual adeno-associated vims (AAVs) is utilized for the delivery of a split-intein prime editor for correction of in vivo pathogenic mutations.
Claims8
A method, comprising:
- a) providing:
- i) a patient having at least one causative mutation in a serpina1 gene allele linked to a genetic disease;
- ii) a fusion protein complex comprising a fusion protein and a prime editing guide RNA molecule (pegRNA);
- wherein the fusion protein comprises a Cas9 nickase and a reverse transcriptase (RT), and wherein the fusion protein comprises an N-terminal c-Myc nuclear localization sequence (NLS) with the amino acid sequence SEQ ID NO:
- 8, an N-terminal NLS bipartite (BP)-SV40 NLS with the amino acid sequence SEQ ID NO:
- 5, a C-terminal variant BP (vBP)-SV40 NLS with the amino acid sequence SEQ ID NO:
- 7, and a SV40 NLS with the amino acid sequence SEQ ID NO:
- 6;
- b) administering said fusion protein complex to said patient;
- and
- c) editing said at least one causative mutation resulting in a conversion to a wild type allele.
8 more elements
Dependencies are inferred from the claim text.