<i>In Vivo</i> RNA Delivery to Hematopoietic Stem and Progenitor Cells <i>via</i> Targeted Lipid Nanoparticles.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36988645.
- Also identified by DOI 10.1021/acs.nanolett.3c00304 and PMC identifier 10103292.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Ex vivo autologous hematopoietic stem cell (HSC) gene therapy has provided new therapies for the treatment of hematological disorders. However, these therapies have several limitations owing to the manufacturing complexities and toxicity resulting from required conditioning regimens. Here, we developed a c-kit (CD117) antibody-targeted lipid nanoparticle (LNP) that, following a single intravenous injection, can deliver RNA (both siRNA and mRNA) to HSCs <i>in vivo</i> in rodents. This targeted delivery system does not require stem cell harvest, culture, or mobilization of HSCs to facilitate delivery. We also show that delivery of Cre recombinase mRNA at a dose of 1 mg kg<sup>-1</sup> can facilitate gene editing to almost all (∼90%) hematopoietic stem and progenitor cells (HSPCs) <i>in vivo</i>, and edited cells retain their stemness and functionality to generate high levels of edited mature immune cells.
Medical subject headings
- Hematopoietic Stem Cell Transplantation