Enhancing the intracellular delivery of antisense oligonucleotides (ASO) : a comparative study of aptamer, vitamin E, and cholesterol ASO conjugates.

ABSTRACT: Antisense oligonucleotides (ASOs) have emerged as powerful tools for gene modulation; however, their clinical application is often hindered by inefficient intracellular delivery. Recent advances suggest that conjugation to biomolecules such as aptamers, lipids, or vitamins may enhance uptake and efficacy. This study investigates the potential of aptamer, vitamin E, and cholesterol-conjugated ASOs to improve delivery and functional activity in cancer cell models. The ASO PNAT524 was conjugated to two DNA aptamers-AS1411 and S2.2-via thiol and triethylene glycol (TEG) linkers, respectively. In parallel, PNAT524 was modified with vitamin E and cholesterol moieties. The conjugates were evaluated for cellular uptake, exon-skipping activity, and cytotoxicity in cancer cell lines. Fluorescence mi

SUBMITTER: Balachandran AA 

PROVIDER: S-EPMC12599544 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature