Main Conference - Day 2 (May 13)Wednesday, 13 May 2026

Current oligonucleotide delivery technologies are not optimized for diverse tissues and therapeutic product profiles. Using multiplexed in vivo screening, we tested thousands of nanobody candidates against hundreds of novel receptor "portals" in mice and non-human primates. These data reveal diverse biodistribution profiles across brain and peripheral tissues, identifying new conjugate partners for improved oligonucleotide delivery.

Effective delivery of genetic medicines to tissues outside the liver is challenging. Here we describe 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.

Ex vivo chimeric antigen receptor (CAR) T-cell therapies have transformed the treatment of B-cell malignancies and shown promise in treating autoimmune diseases. However, they remain limited by complex manufacturing, reliance on viral vectors, and lymphodepleting chemotherapy. NT-001 is 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.

Similarly, while many chronic kidney diseases have defined underlying genetic causes, the kidney has remained inaccessible to genetic medicines due to delivery limitations. We demonstrated 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.

In conclusion, the development of LNP candidates through iterative chemical evolution of ionizable lipids to drive intrinsic tissue tropism, complemented by active targeting approaches, can enable genetic medicines across a wide range of therapeutic applications.