Lipid Nanoparticle-Enabled Intracellular Delivery of Prime Editors

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Prime editing is an advanced gene editing platform with potential to correct almost any disease-causing mutation. As genome editors have evolved, their size and complexity have increased, hindering delivery technologies with low-carrying capacity and endosomal escape. We formulated an array of lipid nanoparticles (LNPs) containing prime editors (PEs). We were able to encapsulate PEs in LNPs and confirmed the presence of PE mRNA and two different guide RNAs using HPLC. In addition, we developed a novel reporter cell line for rapid identification of LNPs suited for prime editing. A 54% prime editing rate was observed with enhanced LNPs (eLNPs) containing the cholesterol analog β-sitosterol at optimal ratios of RNA cargoes. eLNPs displayed a polyhedral morphology and a more fluid membrane state that led to improved endosomal escape, eventually causing onset of editing within 9 h and reaching maximum efficiency after 24 h. Hence, PEs delivered using LNPs can propel a new wave of therapies for many additional targets potentially enabling a range of new applications.

OriginalsprogEngelsk
Artikelnummer65
TidsskriftThe AAPS Journal
Vol/bind25
Udgave nummer4
Antal sider10
ISSN1550-7416
DOI
StatusUdgivet - 2023

Bibliografisk note

© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.

ID: 357847503