NIH R01 · 2024
Developing next generation synthetic nucleic acid analogous for sickle cell disease gene editing
Project Summary There is substantial interest in gene editing as a means to treat human genetic disorders such as sickle cell disease (SCD). Much effort has been focused on targeted nucleases such as CRISPR/Cas9, since site-directed DNA damage strongly promotes homologous recombination (HR). However, clinical application of targeted nucleases is challenged by the risk of off-target cleavage in the genome, which can lead to carcinogenesis. As an alternative, we have shown that chemically modified triplex-forming peptide nucleic acids (TFPs) and donor DNAs (containing corrected base) delivered intravenously (IV) via poly(lactic-co-glycolic) acid (PLGA) nanoparticles into a mouse model of…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.