Delivery of Therapeutic RNA to the Bone Marrow in Multiple Myeloma Using CD38‐Targeted Lipid Nanoparticles

• DOI: 10.1002/advs.202301377
• Publication Date: 2023-05-12T15:31:09Z
• Authors: Dana Tarab‐Ravski; Inbal Hazan‐Halevy; Meir Goldsmith; Lior Stotsky‐Oterin; Dor Breier; Gonna Somu Naidu; Anjaiah Aitha; Yael Diesendruck; Brandon D. Ng; Hagit Barsheshet; Tamar Berger; Iuliana Vaxman; Pia Raanani; Dan Peer
• Keywords: Homing (biology); Therapeutic index

Abstract Multiple myeloma (MM) is a cancer of differentiated plasma cells that occurs in the bone marrow (BM). Despite recent advancements drug development, most patients with MM eventually relapse and disease remains incurable. RNA therapy delivered via lipid nanoparticles (LNPs) has potential to be promising treatment, however, its clinical implementation limited due inefficient delivery non‐hepatic tissues. Here, targeted (t)LNPs designed for payload are presented. The tLNPs consist novel ionizable coated an anti‐CD38 antibody ( α CD38‐tLNPs). To explore their therapeutic potential, it demonstrated LNPs encapsulating small interference (siRNA) against cytoskeleton‐associated protein 5 (CKAP5) lead ≈90% decrease cell viability vitro. Next, new xenograft mouse model employed, which clinically resembles human demonstrates efficient homing BM. Specific CD38‐tLNPs BM‐residing disseminated improvement outcome MM‐bearing mice treated CD38‐tLNPs‐siRNA‐CKAP5 shown. These results underscore therapeutics treatment importance developing effective systems reliable preclinical models.