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Modulating aging-associated phenotypes in keratinocytes using antisense oligonucleotides targeting glycogenes

A study · Nanotheranostics · Oct 23, 2026

What this means

Age-related keratinocyte dysfunction has been associated with altered glycosylation and dysregulated expression of several glycogenes, including St6gal1, St3gal2, and Man1a. Modulation of these aging-associated glycogenes may therefore represent a potential approach for investigating cellular aging phenotypes.

A plain-English summary is on its way. Until then, this is the start of the authors' own summary.

Tested inPeople
Who it was tested in
People
Kind of research
A study

The science

Original title
Modulating aging-associated phenotypes in keratinocytes using antisense oligonucleotides targeting glycogenes.
Authors
Prommalee B, Pilapong C
Journal
Nanotheranostics
Published
Oct 23, 2026
Study type
Study · in humans

Abstract

Age-related keratinocyte dysfunction has been associated with altered glycosylation and dysregulated expression of several glycogenes, including St6gal1, St3gal2, and Man1a. Modulation of these aging-associated glycogenes may therefore represent a potential approach for investigating cellular aging phenotypes. In this study, an in vitro aging-like keratinocyte model exhibiting increased expression of aging-associated glycogenes was established. Antisense oligonucleotides (ASOs) targeting the upregulated glycogenes were designed and evaluated using different oligonucleotide chemistries and delivery systems. Target gene expression, lectin-based glycan profiles, Lgr6 expression, and wound closure were assessed following ASO treatment. Among the ASOs tested, phosphorodiamidate morpholino (PMO)-linked Man1a ASOs demonstrated greater suppression of Man1a mRNA than ASOs targeting St6gal1 or St3gal2. Delivery of PMO-Man1a ASOs using milk-derived nanovesicles (NV) was associated with the greatest reduction in Man1a mRNA levels compared with commercial transfection reagents. Although no significant changes were detected in ConA-reactive mannose-rich glycans, treatment was associated with an increased proportion of Lgr6+ cells and accelerated wound closure in aging-like keratinocytes. Overall, this study provides proof-of-concept evidence that NV-mediated delivery of glycogene-targeting ASOs can modulate selected aging-associated phenotypes in keratinocytes.

Read it on PubMed ↗

Prommalee B, Pilapong C Modulating aging-associated phenotypes in keratinocytes using antisense oligonucleotides targeting glycogenes. Nanotheranostics. 2026. doi:10.7150/ntno.135510. PMID: 42910138. https://pubmed.ncbi.nlm.nih.gov/42910138/

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