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British Medical Bulletin 51:123-137 (1995)
© 1995 The British Council

research-article

Myoblast-based gene therapies

T A Partridge1 and K E Davies2

1MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital London, UK
2Institute of Molecular Medicine, John Radcliffe Hospital Headington, Oxford, UK

Abstract

Recent identification of the genetic causes of several neuromuscular disorders has aroused interest in gene therapy in skeletal muscle. The genetic constitution of skeletal muscle can be altered by a number of means. Myoblasts can be used to introduce new genes, endogenous or exogenous, into muscle fibres during growth and repair. DNA expression-plasmids can be directly transfected into a small proportion of muscle fibres, showing persistent expression despite their lack of genomic integration. Recombinant replication deficient adenoviruses are efficient vectors into myoblasts and developing muscle fibres; again, the introduced constructs show long-term episomal persistence and expression. By contrast, recombinant replication deficient retroviruses efficiently introduce constructs into the genomes of dividing myoblasts which subsequently fuse into muscle fibres. None of the available methods provides a practical solution for therapy of genetic muscle diseases but might be useful for inducing synthesis of therapeutic non-muscle proteins by skeletal muscle.


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