Tuning the tropism and infectivity of SARS-CoV-2 virus-like particles for mRNA delivery DOI Creative Commons
Qi Yang, Bruce A. Davidson, Petar Pajic

et al.

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(5)

Published: Feb. 27, 2025

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 VLP platform for messenger RNA (mRNA) delivery. Cloning nucleocapsid protein upstream M-IRES-E resulted in a three-plasmid (3P) system that displayed ∼7-fold higher viral entry efficiency compared with VLPs formed by co-transfection four plasmids. More than 90% human ACE2-expressing cells could be transduced using these 3P VLPs. Viral tropism programmed switching glycoproteins from other strains, including betacoronaviruses and vesicular stomatitis virus G protein. An infectious two-plasmid was also advanced where one vector carried surface glycoprotein second remaining SARS-CoV-2 structural proteins reporter gene. engineered carry up transgenes, functional Cas9 mRNA genome editing. Gene editing specific target cell types feasible modifying tropism. Successful delivery mouse lungs suggests can overcome natural biological barriers enable pulmonary gene Overall, study describes advancement robust both vitro vivo.

Language: Английский

Tuning the tropism and infectivity of SARS-CoV-2 virus-like particles for mRNA delivery DOI Creative Commons
Qi Yang, Bruce A. Davidson, Petar Pajic

et al.

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(5)

Published: Feb. 27, 2025

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 VLP platform for messenger RNA (mRNA) delivery. Cloning nucleocapsid protein upstream M-IRES-E resulted in a three-plasmid (3P) system that displayed ∼7-fold higher viral entry efficiency compared with VLPs formed by co-transfection four plasmids. More than 90% human ACE2-expressing cells could be transduced using these 3P VLPs. Viral tropism programmed switching glycoproteins from other strains, including betacoronaviruses and vesicular stomatitis virus G protein. An infectious two-plasmid was also advanced where one vector carried surface glycoprotein second remaining SARS-CoV-2 structural proteins reporter gene. engineered carry up transgenes, functional Cas9 mRNA genome editing. Gene editing specific target cell types feasible modifying tropism. Successful delivery mouse lungs suggests can overcome natural biological barriers enable pulmonary gene Overall, study describes advancement robust both vitro vivo.

Language: Английский

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