Tuning the tropism and infectivity of SARS-CoV-2 virus-like particles for mRNA delivery.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus-like particles (VLPs) are ∼100-nm-sized bioinspired mimetics of the authentic virus. We undertook molecular engineering to optimize the VLP platform for messenger RNA (mRNA) delivery. Cloning the nucleocapsid protein upstream of M-IRES-E resulted in a three-plasmid (3P) VLP system that displayed ∼7-fold higher viral entry efficiency compared with VLPs formed by co-transfection with four plasmids. More than 90% of human ACE2-expressing cells could be transduced using these 3P VLPs. Viral tropism could be programmed by switching glycoproteins from other viral strains, including other betacoronaviruses and the vesicular stomatitis virus G protein. An infectious two-plasmid VLP system was also advanced where one vector carried

SUBMITTER: Yang Q 

PROVIDER: S-EPMC11879429 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature