Generation of a caged lentiviral vector through an unnatural amino acid for photo-switchable transduction

Nucleic Acids Research
Yan WangDemin Zhou

Abstract

Application of viral vectors in gene delivery is attracting widespread attention but is hampered by the absence of control over transduction, which may lead to non-selective transduction with adverse side effects. To overcome some of these limitations, we proposed an unnatural amino acid aided caging-uncaging strategy for controlling the transduction capability of a viral vector. In this proof-of-principle study, we first expanded the genetic code of the lentiviral vector to incorporate an azido-containing unnatural amino acid (Nϵ-2-azidoethyloxycarbonyl-l-lysine, NAEK) site specifically within a lentiviral envelope protein. Screening of the resultant vectors indicated that NAEK incorporation at Y77 and Y116 was capable of inactivating viral transduction upon click conjugation with a photo-cleavable chemical molecule (T1). Exposure of the chimeric viral vector (Y77-T1) to UVA light subsequently removed the photo-caging group and restored the transduction capability of lentiviral vector both in vitro and in vivo. Our results indicate that the use of the photo-uncage activation procedure can reverse deactivated lentiviral vectors and thus enable regulation of viral transduction in a switchable manner. The methods presented here m...Continue Reading

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Citations

Feb 23, 2020·Frontiers in Aging Neuroscience·Alexandre IarkovValentina Echeverria
Oct 8, 2020·Biomaterials Science·Kübra Kaygisiz, Christopher V Synatschke
Feb 10, 2021·Signal Transduction and Targeted Therapy·Jote T BulchaGuangping Gao

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Methods Mentioned

BETA
transfection
Assay
flow cytometry
electrophoresis
fluorescence imaging
PCR
Fluorescence
confocal microscopy
bioluminescence

Software Mentioned

Graphpad Prism

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