Optimizing Lipid Nanoparticles for Delivery in Primates
© 2023 Genevant Sciences Corporation. Advanced Materials published by Wiley-VCH GmbH.
| Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 35(2023), 26 vom: 27. Juni, Seite e2211420 |
|---|---|
| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2023
|
| Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
| Schlagworte: | Journal Article PEG shielding lipid nanoparticles nanotechnology nucleic acid particle size potency translation therapeutics Lipid Nanoparticles Lipids mehr... |
| Zusammenfassung: | © 2023 Genevant Sciences Corporation. Advanced Materials published by Wiley-VCH GmbH. Lipid nanoparticles (LNPs) are clinically proven to successfully deliver both small interfering RNA (siRNA) therapeutics and larger mRNA payloads for prophylactic vaccine applications. Non-human primates (NHPs) are generally considered to be the most predictive of human responses. However, for ethical and economic reasons, LNP compositions have historically been optimized in rodents. It has been difficult to translate LNP potency data from rodents to NHPs for intravenously (IV) administered products in particular. This presents a major challenge for preclinical drug development. An attempt to investigate LNP parameters, which have historically been optimized in rodents, is carried out, and seemingly innocuous changes are found to result in large potency differences between species. For example, the ideal particle size for NHPs (50-60 nm) is found to be smaller than for rodents (70-80 nm). Surface chemistry requirements are also different, with almost double the amount of poly(ethylene glycol) (PEG)-conjugated lipid needed for maximal potency in NHPs. By optimizing these two parameters, approximately eight-fold increase in protein expression from intravenously administered messenger RNA (mRNA)-LNP in NHP is gained. The optimized formulations are well tolerated when administered repeatedly with no loss of potency. This advancement enables the design of optimal LNP products for clinical development |
|---|---|
| Beschreibung: | Date Completed 29.06.2023 Date Revised 29.06.2023 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-4095 |
| DOI: | 10.1002/adma.202211420 |