Modulating aging-associated phenotypes in keratinocytes using antisense oligonucleotides targeting glycogenes.
- 1Laboratory of BioMolecular Imaging, Molecular and Cellular Biology, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.
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.
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BibTeX
@article{prommalee2026modulating,
title = {{Modulating aging-associated phenotypes in keratinocytes using antisense oligonucleotides targeting glycogenes.}},
author = {Bhanubhong Prommalee and Chalermchai Pilapong},
journal = {Nanotheranostics},
year = {2026},
month = oct,
doi = {10.7150/ntno.135510},
url = {https://europepmc.org/article/MED/42910138},
note = {CC BY},
}
RIS
TY - JOUR
TI - Modulating aging-associated phenotypes in keratinocytes using antisense oligonucleotides targeting glycogenes.
AU - Bhanubhong Prommalee
AU - Chalermchai Pilapong
PY - 2026
DA - 2026/10/09
JO - Nanotheranostics
DO - 10.7150/ntno.135510
UR - https://europepmc.org/article/MED/42910138
AB - 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.
SN - 2206-7418
ER -