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Plasma-membrane proteins in human skeletal muscle for targeted drug delivery: An annotated resource

Year: 2026
Type: review
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.
DOI: 10.1016/j.omtn.2026.103115
Language: English
Open Access status: gold
Estimated APC paid: $3,900
OpenAlex ID: W7214438772
FWCI:
Cites: 132
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Related to: 10