1022-7954/01/3708- $25.00 © 2001
Russian Journal of Genetics, Vol. 37, No. 8, 2001, pp. 868–875. Translated from Genetika, Vol. 37, No. 8, 2001, pp. 1046–1054.
Original Russian Text Copyright © 2001 by V. Baranov, A. Baranov, Zelenin.
Duchenne muscular dystrophy (DMD) is among the
most common X-linked hereditary human diseases. Its
incidence rate is about 1 : 5000 of newborn males.
DMD is caused by a mutation in the gene of dystrophin
(D), a structural protein of the sarcolemma [1, 2]. If this
protein is completely absent, or only its functionally
abortive forms are present in the muscle ﬁber, the mem-
brane is disrupted and degeneration of the ﬁbers of the
skeletal muscles, diaphragm, and heart occurs. The D
gene is the largest human gene known thus far (2.4 Mb).
It accounts for almost 0.1% of the human genome, con-
tains 85 exons, and encodes a 14-kb mRNA [1, 3, 4].
The main product of its expression, muscle D, has a
molecular weight of 427 kDa. The protein D binds with
F actin, the main component of the intracellular system
of ﬁlaments, at its N end and with dystro- and sarcogly-
cans (a group of dystrophin-associated glycoproteins)
at its C end, thus stabilizing the sarcolemma of the mus-
cle ﬁber. The system of membrane proteoglycans links
D with laminin, the main protein of extracellular
matrix. Mutations in the D gene cause either a complete
absence of D or a considerably decreased amount of it
(DMD or Becker muscular dystrophy, respectively),
which disturbs the function of muscle ﬁbers. An
increased membrane permeability or physical disrup-
tion of membranes, which is characteristic of prene-
crotic and necrotic ﬁbers, causes leakage of muscle
enzymes into blood serum. At the initial stages of the
disease, muscle degeneration is compensated for by
active regeneration of myoﬁbrils due to division and
fusion of myogenic satellite cells. However, regenera-
tion becomes less effective with age. Muscle cells
become incapable of maintaining the homeostasis,
degenerate, and are gradually replaced by connective
tissue. The progressive loss of the muscle mass causes
death of the affected persons due to heart or diaphragm
failure at ages below 20 years .
DMD: BIOLOGICAL MODELS
Most studies aimed at developing the gene therapy
(GT) of DMD are conducted on muscles with sponta-
neous or induced mutations in the D gene. The ﬁrst
DMD model was found when studying biochemical
abnormalities of blood in C57BL/10J inbred mice .
 identiﬁed a nonsense mutation
in exon 23 of the D gene in mdx mice and conﬁrmed
that this mouse strain might serve as a biological model
of DMD. To date, several mouse strains carrying muta-
tions in the D gene have been obtained. The disease
severity and pathogenesis in mdx52 mice, which carry
the deletion of exon 52 , and dko mice, which carry
mutations in the D gene and the gene of utrophin (U; an
autosomal analogue of D) , are the most similar to
those observed in human DMD.
The disease caused by mutations in the D gene of
golden retrievers is most similar to the human DMD
with respect to the severity and clinical manifestations
[10, 11]. These dogs are recommended as a model for
the last stage of preclinical tests of the GT of DMD.
One more DMD model in dogs carrying a deletion in
the X-chromosome short arm has been recently
The Current State and Prospects of the Gene Therapy
of Duchenne Muscular Dystrophy Worldwide and in Russia
V. S. Baranov
, A. N. Baranov
, and A. V. Zelenin
Ott Institute of Obstetrics and Gynecology, Russian Academy of Medical Sciences, St. Petersburg, 199034 Russia;
fax: (812)328-04-87; e-mail: firstname.lastname@example.org
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
Received March 22, 2001
—Failure of drug therapy of Duchenne muscular dystrophy (DMD) stimulated intense search for ade-
quate methods of gene therapy (GT) which would ensure effective delivery of the dystrophin (D) gene, its long-
term persistence in transfected cells, and its expression in muscle ﬁbers. The main results of the experimental
GT of DMD with the use of viral and nonviral delivery of the D gene into muscles of biological models are
discussed. Delivery of a mini-gene of D with a speciﬁc muscle promoter using a modiﬁed adenoassociated virus
is currently the most promising method, which will soon be available for clinical trials. The main results of the
studies on the DMD GT in Russia are summarized. The results of experiments on genetic transfection of mdx
mice with marker genes and various constructions with the D gene are outlined. The genes are delivered into
muscles by means of gene gun, electroporation, viral oligopeptides, liposomes, microspheres, lactoferine, and
other nonviral vehicles. It is emphasized that consolidation of funds and efforts of all Russian laboratories deal-
ing with gene and cell therapy of DMD are necessary to complete the experiments and start clinical trials.