申请人:Yale University
公开号:US11136597B2
公开(公告)日:2021-10-05
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.
本文公开了用于增强靶向基因编辑的组合物和方法及其使用方法。在最优选的实施方案中,基因编辑是利用基因编辑组合物,如三聚体形成寡核苷酸、CRISPR、锌指核酸酶、TALENS或其他,结合基因修饰增效剂,如干细胞因子(SCF)、CHK1或ATR抑制剂,或它们的组合来进行的。一种特别优选的基因编辑组合物是在γ位被取代的三重形成肽核酸(PNA),以增加 DNA 结合亲和力。此外,还提供了用于细胞内递送基因编辑组合物的纳米颗粒组合物,尤其适用于体内应用。