title: Cellular delivery and photochemical activation of antisense agents through a nucleobase caging strategy.
abstract: Antisense oligonucleotides are powerful tools to regulate gene expression in cells and model organisms. However, a transfection or microinjection is typically needed for efficient delivery of the antisense agent. We report the conjugation of multiple HIV TAT peptides to a hairpin-protected antisense agent through a light-cleavable nucleobase caging group. This conjugation allows for the facile delivery of the antisense agent without a transfection reagent, and photochemical activation offers precise control over gene expression. The developed approach is highly modular, as demonstrated by the conjugation of folic acid to the caged antisense agent. This enabled targeted cell delivery through cell-surface folate receptors followed by photochemical triggering of antisense activity. Importantly, the presented strategy delivers native oligonucleotides after light-activation, devoid of any delivery functionalities or modifications that could otherwise impair their antisense activity.
authors.affiliation: North Carolina State University , Department of Chemistry, Raleigh, North Carolina 27695, United States.
authors.forename: Jeane M
authors.initials: JM
authors.lastname: Govan
authors.forename: Rajendra
authors.initials: R
authors.lastname: Uprety
authors.forename: Meryl
authors.initials: M
authors.lastname: Thomas
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Lusic
authors.forename: Mark O
authors.initials: MO
authors.lastname: Lively
authors.forename: Alexander
authors.initials: A
authors.lastname: Deiters
mesh_terms: D001483:Base Sequence; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D008027:Light; D008954:Models, Biological; D015394:Molecular Structure; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics
chemical_list: D016376:Oligonucleotides, Antisense; D054322:tat Gene Products, Human Immunodeficiency Virus
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