US 11,136,597 B2 · Compositions for enhancing targeted gene editing and methods of use thereof

Abstract

Compositions and methods for enhancing targeted gene editing and methods of use thereof are disclosed. In the most preferred embodiments, gene editing is carried out utilizing a gene editing composition such as triplex-forming oligonucleotides, CRISPR, zinc finger nucleases, TALENS, or others, in combination with a gene modification potentiating agent such as stem cell factor (SCF), a CHK1 or ATR inhibitor, or a combination thereof. A particular preferred gene editing composition is triplex-forming peptide nucleic acids (PNAs) substituted at the γ position for increased DNA binding affinity. Nanoparticle compositions for intracellular delivery of the gene editing composition are also provided and particular advantageous for use with in vivo applications.

Claims30

Dependent claims

A method of modifying the genomes of CD117+ cells comprising contacting the CD117+ cells with an effective amount of

(i) a gene editing potentiating agent selected from the group consisting of receptor tyrosine kinase C-kit ligands, ATR-Chk1 cell cycle checkpoint pathway inhibitors, and heat shock protein 90 inhibitors (HSP90i), and
(ii) a gene editing technology that can induce genomic modification through a mechanism comprising a DNA repair pathway endogenous to the CD117+ cells,
to modify the genomes of the CD117+ cells contacted with both (i) and (ii) at a higher frequency than an equivalent population of cells contacted with (ii) in the absence of (i).

Dependencies are inferred from the claim text.

Compositions for enhancing targeted gene editing and methods of use thereof

Life of this patent

Compositions for enhancing targeted gene editing and methods of use thereof

Life of this patent

Abstract

Claims30