Unknown

Dataset Information

0

Self-Assembled DNA-PEG Bottlebrushes Enhance Antisense Activity and Pharmacokinetics of Oligonucleotides.


ABSTRACT: Herein, we report a novel strategy to enhance the antisense activity and the pharmacokinetics of therapeutic oligonucleotides. Through the DNA hybridization chain reaction, DNA hairpins modified with poly(ethylene glycol) (PEG) form a bottlebrush architecture consisting of a double-stranded DNA backbone, PEG side chains, and antisense overhangs. The assembled structure exhibits high PEG density on the surface, which suppresses unwanted interactions between the DNA and proteins (e.g., enzymatic degradation) while allowing the antisense overhangs to hybridize with the mRNA target and thereby deplete target protein expression. We show that these PEGylated bottlebrushes targeting oncogenic KRAS can achieve much higher antisense efficacy compared with unassembled hairpins with or without PEGylation and can inhibit the proliferation of lung cancer cells bearing the G12C mutant KRAS gene. Meanwhile, these structures exhibit elevated blood retention times in vivo due to the biological stealth properties of PEG and the high molecular weight of the overall assembly. Collectively, this self-assembly approach bears the characteristics of a simple, safe, yet highly translatable strategy to improve the biopharmaceutical properties of therapeutic oligonucleotides.

SUBMITTER: Wang Y 

PROVIDER: S-EPMC8110734 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC5568898 | biostudies-literature
| S-EPMC10899043 | biostudies-literature
| S-EPMC8293047 | biostudies-literature
| S-EPMC2783907 | biostudies-literature
| S-EPMC6736852 | biostudies-literature
| S-EPMC5971383 | biostudies-literature
| S-EPMC7367172 | biostudies-literature
| S-EPMC6276310 | biostudies-literature
| S-EPMC10302603 | biostudies-literature
| S-EPMC6212795 | biostudies-literature