N. Murthy

Chemically modified CRISPR enzymes for multi-organ genome editing in vivo

Delivery remains the main obstacle to the development of in vivo genome editing therapies. CRISPR ribonucleoproteins confer high editing activity with transient exposure but lack intrinsic cell entry and targeting. Here we introduce PERCEPT, a delivery platform featuring reversible, covalent modification of CRISPR enzy...

Charge-switching ionizable lipids lower the toxicity of lipid nanoparticles.

Lipid nanoparticles (LNPs) have great potential as nucleic acid delivery vehicles; however, they trigger the production of inflammatory cytokines, which limits their medical applications. Developing non-inflammatory LNPs is challenging because the LNP's ionizable lipid and the process of endosomal disruption are the ma...

LNP-mediated BCL11A Editing Corrects Sickling Phenotypes and Preserves HSPC Fitness Compared to Electroporation

Although RNP electroporation achieves higher CRISPR editing rates, it reduces HSPC recovery and RBC differentiation; conversely, mRNA-LNP delivery achieves modest rates while preserving HSPC fitness, progenitor expansion, and RBC enucleation efficiencies.

LNP-mediated BCL11A Editing Corrects Sickling Phenotypes and Preserves HSPC Fitness Compared to Electroporation

A lipid nanoparticle platform for high yield CRISPR-targeted homology directed repair enables fully non-viral CAR T cell generation