In Vivo Generation of Functional CD8+ CAR T-Cells & Renal Gene Editing Driven by Distinct & Selective LNP Tropism
- Describing a modular LNP platform that facilitates functional delivery of nucleic acids to extra-hepatic cell types, including immune cells, kidney, and others, and has the potential to enable a wide range of therapeutic applications
- Showcasing NT-001, an in vivo CAR T-cell therapy utilizing a cell-specific binder targeting LNPs to cytotoxic T-cells. In humanized CD34⁺ mice and non-human primates (NHPs), two systemic administrations achieved full B-cell depletion across tissues, transient CAR expression, and a clinical chemistry profile consistent with a tolerable LNP.
- Demonstrating that novel kidney-tropic LNPs achieve preferential delivery to renal cell populations following intravenous administration. In mice, reporter expression exceeded 50% in Nephrin-positive cells, while Cas9 mRNA / sgRNA LNPs achieved efficient editing in the kidney, with editing efficiencies surpassing 60% in disease-relevant podocytes and proximal tubule cells as observed by spatial transcriptomics. Furthermore, kidney tropism was confirmed in NHPs