Gene therapy approaches to regenerating the musculoskeletal system

Christopher H Evans, Johnny Huard

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Injuries to the musculoskeletal system are common, debilitating and expensive. In many cases, healing is imperfect, which leads to chronic impairment. Gene transfer might improve repair and regeneration at sites of injury by enabling the local, sustained and potentially regulated expression of therapeutic gene products; such products include morphogens, growth factors and anti-inflammatory agents. Proteins produced endogenously as a result of gene transfer are nascent molecules that have undergone post-translational modification. In addition, gene transfer offers particular advantages for the delivery of products with an intracellular site of action, such as transcription factors and noncoding RNAs, and proteins that need to be inserted into a cell compartment, such as a membrane. Transgenes can be delivered by viral or nonviral vectors via in vivo or ex vivo protocols using progenitor or differentiated cells. The first gene transfer clinical trials for osteoarthritis and cartilage repair have already been completed. Various bone-healing protocols are at an advanced stage of development, including studies with large animals that could lead to human trials. Other applications in the repair and regeneration of skeletal muscle, intervertebral disc, meniscus, ligament and tendon are in preclinical development. In addition to scientific, medical and safety considerations, clinical translation is constrained by social, financial and logistical issues.

Original languageEnglish (US)
Pages (from-to)234-242
Number of pages9
JournalNature Reviews Rheumatology
Volume11
Issue number4
DOIs
StatePublished - Apr 1 2015

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Musculoskeletal System
Genetic Therapy
Genes
Regeneration
Untranslated RNA
Intervertebral Disc
Wounds and Injuries
Post Translational Protein Processing
Transgenes
Ligaments
Osteoarthritis
Tendons
Cartilage
Intercellular Signaling Peptides and Proteins
Skeletal Muscle
Proteins
Anti-Inflammatory Agents
Transcription Factors
Clinical Trials
Safety

ASJC Scopus subject areas

  • Rheumatology

Cite this

Gene therapy approaches to regenerating the musculoskeletal system. / Evans, Christopher H; Huard, Johnny.

In: Nature Reviews Rheumatology, Vol. 11, No. 4, 01.04.2015, p. 234-242.

Research output: Contribution to journalArticle

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