Plasma-membrane proteins in human skeletal muscle for targeted drug delivery: An annotated resource
- 1Department of Science and Environment, Roskilde University, Roskilde, Denmark
- 2Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Aarhus, Denmark
- 3Department of Science and Environment, Roskilde University, Roskilde, Denmark; Corresponding author: Louise T. Dalgaard, Department of Science and Environment, Roskilde University, Roskilde, Denmark.
Abstract
Skeletal muscle is essential for metabolic regulation, energy homeostasis, and physical function. Its dysfunction contributes to disorders such as type 2 diabetes, muscular dystrophies, sarcopenia, cachexia, and muscle wasting linked to aging, cancer, and immobilization. Despite advances in RNA-based therapeutics, achieving efficient and selective delivery to skeletal muscle remains a major translational barrier. Targeting muscle-enriched cell-surface proteins represents a promising strategy to improve therapeutic specificity while limiting systemic exposure. Here, we combine a systematic literature review with database-driven analyses to identify and prioritize skeletal muscle-enriched plasma membrane proteins as candidate entry points for targeted delivery. The review summarizes current targeting approaches, highlighting their strengths and limitations. In parallel, integrative mining of the Human Protein Atlas, Genotype-Tissue Expression (GTEx), and CellxGene datasets identified 76 high-confidence skeletal muscle-enriched membrane-associated proteins. These were further functionally annotated and ranked using multi-parameter criteria, including relevance to internalization and suitability for nucleic acid-based delivery. In addition, we discuss potential disease contexts in which to employ these. Together, these analyses generate a curated resource of candidate targets and provide a conceptual framework for developing next-generation delivery platforms for RNA therapeutics and other modalities aimed at skeletal muscle across a broad range of muscle-related diseases.
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BibTeX
@article{stanojevic2026plasmamembrane,
title = {{Plasma-membrane proteins in human skeletal muscle for targeted drug delivery: An annotated resource}},
author = {Nemanja Stanojević and Jørgen Kjems and Louise T. Dalgaard},
journal = {Molecular Therapy: Nucleic Acids},
year = {2026},
month = sep,
doi = {10.1016/j.omtn.2026.103115},
url = {https://doi.org/10.1016/j.omtn.2026.103115},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Plasma-membrane proteins in human skeletal muscle for targeted drug delivery: An annotated resource
AU - Nemanja Stanojević
AU - Jørgen Kjems
AU - Louise T. Dalgaard
PY - 2026
DA - 2026/09/26
JO - Molecular Therapy: Nucleic Acids
DO - 10.1016/j.omtn.2026.103115
UR - https://doi.org/10.1016/j.omtn.2026.103115
AB - Skeletal muscle is essential for metabolic regulation, energy homeostasis, and physical function. Its dysfunction contributes to disorders such as type 2 diabetes, muscular dystrophies, sarcopenia, cachexia, and muscle wasting linked to aging, cancer, and immobilization. Despite advances in RNA-based therapeutics, achieving efficient and selective delivery to skeletal muscle remains a major translational barrier. Targeting muscle-enriched cell-surface proteins represents a promising strategy to improve therapeutic specificity while limiting systemic exposure. Here, we combine a systematic literature review with database-driven analyses to identify and prioritize skeletal muscle-enriched plasma membrane proteins as candidate entry points for targeted delivery. The review summarizes current targeting approaches, highlighting their strengths and limitations. In parallel, integrative mining of the Human Protein Atlas, Genotype-Tissue Expression (GTEx), and CellxGene datasets identified 76 high-confidence skeletal muscle-enriched membrane-associated proteins. These were further functionally annotated and ranked using multi-parameter criteria, including relevance to internalization and suitability for nucleic acid-based delivery. In addition, we discuss potential disease contexts in which to employ these. Together, these analyses generate a curated resource of candidate targets and provide a conceptual framework for developing next-generation delivery platforms for RNA therapeutics and other modalities aimed at skeletal muscle across a broad range of muscle-related diseases.
SN - 2162-2531
ER -