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、CRI
SPR、
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。