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Peer-reviewedCC BYCell biomaterials

miRNA delivery via nanowires restores functional responses in aged T cells

  • Zhonghao Dai1
  • Shaylyn Grier1
  • Zhe Zhong2
  • Ameya Dravid1
  • Joscelyn Mejías1
  • Jean L. Koff3
  • Andrés J. García1
  • Ankur Singh1
  1. 1Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
  2. 2Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA 30332, USA
  3. 3Winship Cancer Center, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA
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Abstract

SUMMARY: Aging reshapes CD8+ T cell immunity by depleting naive populations, narrowing repertoire diversity, and promoting dysfunctional states, thereby weakening responses to infection or vaccination. This study presents a polyethyleneimine (PEI)-functionalized silicon nanowire platform for high-viability, non-viral delivery of single or multiplexed microRNAs (miRNAs) into resting aged CD8+ T cells. Nanowires enable transient modulation of transcriptional programs governing T cell activation, metabolism, proliferation, and differentiation. Delivering a single miRNA influences early activation and differentiation stages, while multiplexed miRNA delivery leads to a broader boost in activation responses, effector functions, metabolic health, and cell proliferation. In vivo, ex vivo-treated aged CD8+ T cells exhibit enhanced early effector priming following antigen exposure. Similarly, in aged human CD8+ T cells, multiplexed miRNA enhances activation and cytotoxic responses and sustains an effector-primed state during early activation and expansion. This method consistently improves function across donors aged from healthy individuals to those with current or past cancer.

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Cite

BibTeXRIS
BibTeX
@article{dai2026mirna,
  title = {{miRNA delivery via nanowires restores functional responses in aged T cells}},
  author = {Zhonghao Dai and Shaylyn Grier and Zhe Zhong and Ameya Dravid and Joscelyn Mejías and Jean L. Koff and Andrés J. García and Ankur Singh},
  journal = {Cell biomaterials},
  year = {2026},
  month = jul,
  doi = {10.1016/j.celbio.2026.100514},
  url = {https://europepmc.org/article/PMC/PMC13730167},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - miRNA delivery via nanowires restores functional responses in aged T cells
AU  - Zhonghao Dai
AU  - Shaylyn Grier
AU  - Zhe Zhong
AU  - Ameya Dravid
AU  - Joscelyn Mejías
AU  - Jean L. Koff
AU  - Andrés J. García
AU  - Ankur Singh
PY  - 2026
DA  - 2026/07/03
JO  - Cell biomaterials
DO  - 10.1016/j.celbio.2026.100514
UR  - https://europepmc.org/article/PMC/PMC13730167
AB  - SUMMARY: Aging reshapes CD8+ T cell immunity by depleting naive populations, narrowing repertoire diversity, and promoting dysfunctional states, thereby weakening responses to infection or vaccination. This study presents a polyethyleneimine (PEI)-functionalized silicon nanowire platform for high-viability, non-viral delivery of single or multiplexed microRNAs (miRNAs) into resting aged CD8+ T cells. Nanowires enable transient modulation of transcriptional programs governing T cell activation, metabolism, proliferation, and differentiation. Delivering a single miRNA influences early activation and differentiation stages, while multiplexed miRNA delivery leads to a broader boost in activation responses, effector functions, metabolic health, and cell proliferation. In vivo, ex vivo-treated aged CD8+ T cells exhibit enhanced early effector priming following antigen exposure. Similarly, in aged human CD8+ T cells, multiplexed miRNA enhances activation and cytotoxic responses and sustains an effector-primed state during early activation and expansion. This method consistently improves function across donors aged from healthy individuals to those with current or past cancer.
SN  - 3050-5623
ER  -