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T R A N S L AT I O N A L G E N E T I C S
delivery to all muscle, which constitutes

Therapy for Duchenne muscular ~35% of the body mass, is a considerable

hurdle. Many therapies work well in the mdx

dystrophy: renewed optimism from

mouse — the frequently used animal model
of the disease, which has a stop codon in
exon 23 of the dystrophin gene — and the
genetic approaches golden retriever muscular dystrophy dog
models of the disease. In these models, point
mutations result in the absence of dystro‑
Rebecca J. Fairclough, Matthew J. Wood and Kay E. Davies phin, but efficacy will need to be improved
in patients to lead to significant disease
Abstract | Duchenne muscular dystrophy (DMD) is a devastating progressive
modification.
disease for which there is currently no effective treatment except palliative Just as the identification of the dystro‑
therapy. There are several promising genetic approaches, including viral delivery phin gene was one of the first successes of
of the missing dystrophin gene, read-through of translation stop codons, exon positional cloning, the pioneering genetic
skipping to restore the reading frame and increased expression of the approaches now entering the clinic for DMD
(TABLE 1) are also applicable to other diseases.
compensatory utrophin gene. The lessons learned from these approaches will be
applicable to many other disorders.
Viral gene therapy
Direct replacement of the missing pro‑
Duchenne muscular dystrophy (DMD) is a DMD. In‑frame deletions result in a milder tein can be effected by viral gene therapy,
relentless, X‑linked recessive muscle-wasting form of the disease, Becker muscular dys‑ although this strategy has had a cheq‑
disease with one of the highest known rates trophy (BMD), in which patients express a uered history when applied to other dis‑
of new mutations, meaning that many cases truncated, partially functional dystrophin. orders because of deaths in clinical trials
in the clinic have no previous family his‑ Symptoms of BMD range from loss of ambu‑ and immune reactions to viral proteins6.
tory 1. The gene responsible for the disease lation in the late teens to manifestation only However, this approach is now coming of
encodes the large cytoskeletal structural as a cardiomyopathy in patients who live age as more is understood about the viral
protein dystrophin, which is absent or pre‑ into their 80s. genome and the relationship with its host.
sent at very low levels in patients with DMD. No effective treatment exists for DMD. Adeno-associated virus (AAV) vectors in
Dystrophin is essential for muscle mem‑ Although there are numerous pharmaco‑ particular are providing spectacular results
brane stability as it provides an important logical strategies that delay symptoms by for eye disorders7, and expression of the
link between the dystrophin-associated pro‑ tackling the secondary effects of DMD, transgene has been reported in a haemophilia
tein complex (DAPC) at the muscle mem‑ many are only partially effective because B patient 10 years after gene transfer into
brane and the actin cytoskeleton2 (FIG. 1). they treat just one aspect of the pathogenesis, muscle8. In DMD, the challenge has been the
Boys affected by DMD are usually diagnosed and they may be toxic in the longer term4. large size of the mRNA (14 kb) and the need
at 3–5 years and go into a wheelchair at Thus there has been great interest in devel‑ to target all muscles. Dystrophin mini- or
about 12 years of age. Abnormal cardiac oping genetic approaches to treat the disease micro-genes (~6 kb) have been designed on
function observed by magnetic resonance that tackle the primary defect. This article the basis of the mutant form of the gene car‑
imaging (MRI) or echocardiography is usu‑ summarizes recent progress with these ried in a mildly affected patient with BMD.
ally seen in early teens but may be observed genetic approaches to therapy, including This form has a large in‑frame rod domain
as early as age 8. Patients usually die in their both the ‘traditional’ gene therapy approach deletion and fits into AAV vectors even when
20s from respiratory or heart failure, and of direct replacement of the protein, and muscle-specific promoters are incorporated9.
a minority of patients also show mental newer approaches involving the manipula‑ These mini-genes have been optimized to
impairment. tion of the cellular machinery at the level include motifs such as neuronal nitric oxide
The full-length dystrophin gene (FIG. 2Aa) of gene transcription, mRNA processing or synthase (nNOS) binding sites10.
is predominantly expressed in skeletal translation. The challenge is that any effec‑ Although in mice no cellular immune
and cardiac muscle with smaller amounts tive therapy will need to restore dystrophin responses against either the capsid proteins
expressed in the brain. Sixty-five per cent of in both skeletal and heart muscle, and the or transgene products have been observed
the mutations are deletions of the whole or treatment would need to be life-long. Studies using these mini-genes, studies in larger ani‑
a part of the gene. There are two hotspots of patients with X‑linked dilated cardio‑ mals and humans have resulted in variable
for deletions within the gene sequence3. myopathy show that dystrophin levels as immunological outcomes. In a recent clini‑
Deletions that leave the mRNA out‑of‑frame low as 30% in skeletal muscle are sufficient cal trial using AAV delivery to the biceps of
abolish protein production and lead to to prevent muscle weakness5. Nevertheless, a mini-dystrophin gene under the control

NATURE REVIEWS | GENETICS VOLUME 14 | JUNE 2013 | 373

© 2013 Macmillan Publishers Limited. All rights reserved

PROGRESS
Extracellular matrix
Sarcoglycan
complex
Sarcolemma
Sarcospan
Cytoplasm
nNOS binding sites
Actin filaments Dystrophin
Figure 1 | The dystrophin-associated protein complex.  DystrophinNature
between the internal cytoskeleton and the extracellular matrix. Neuronal nitric oxide synthase
(nNOS) binds to α-syntrophin but also has a binding site in repeat 17 of the rod domain of dystrophin
(see FIG. 2A for details of dystrophin domains). αDG, α-dystroglycan; βDG, β-dystroglycan.
of the cytomegalovirus (CMV) promoter,
an immune response directed against the
transgene product was observed11. However,
a trial delivering an α‑sarcoglycan transgene
to patients with limb girdle muscular dys‑
trophy (LGMD) did not evoke an immune
response. This may have been because the
transgene was under the control of a muscle-
specific promoter 12. In the DMD trial, it was
also proposed that rare dystrophin-positive
revertant fibres, which may have resulted
from a mutation at a second site or from
alternative splicing, could express an immu‑
nogenic epitope never previously seen by the
patient 13. These data emphasize the impor‑
tance of pre-screening patients for immune
responses to dystrophin before admission
into trials. In addition, more needs to be
understood regarding why certain patients
have T cells that are activated in response to
dystrophin epitopes.
Little is known about how long dystro‑
phin expression will be sustained after a sin‑
gle administration in humans, and repeated
treatment may be necessary. Clinical trials
in patients with LGMD have highlighted
the need to be vigilant about pre-existing
immunity to the AAV capsid, although it is
possible to use different AAV serotypes in
successive treatments.
Although more work is needed on vector
design and the use of muscle-specific pro‑
moters to minimize any immune response,
the local delivery trials have been very
informative and show that viral therapy
is generally safe with no reported adverse
374 | JUNE 2013 | VOLUME 14 www.nature.com/reviews/genetics
α2 Laminin 2
β1 γ1
αDG Dystroglycans
δ γ β α βDG
β1 Syntrophins
β2
α
α-Dystrobrevin
acts asReviews
an important link
| Genetics
events. In future trials, transient immuno‑
suppression may prove to be highly effective
for the systemic delivery of viral vectors,
as has been shown for the dog model of
DMD14. The use of utrophin (FIG. 2Ad) rather
than dystrophin mini-genes would avoid the
immune response to dystrophin. However,
even if the immune response can be mini‑
mized, delivery to all muscles in the body
remains an important challenge with viral
therapy for DMD.
Termination codon read-through
Premature termination codon mutations
occur in ~15% of patients with DMD (see
Leiden Muscular Dystrophy Pages), and
therefore these boys could potentially be
treated by drugs that promote read-through.
Aminoglycosides restore protein transla‑
tion in cell assays, but many of these have
long-term toxic effects15. PTC Therapeutics
have screened for drugs that promote read-
through of stop codons in DMD cell lines
and the mdx mouse16. Ataluren (FIG. 2Ac) is
the first drug in this class, but initial human
trials have been disappointing. Dystrophin
expression appeared to be increased in most
patients but no clear quantitative analyses
were presented for this Phase IIa clinical
study 17. The clinical endpoint for these trials
was the six-minute walk test (6MWT)17,18,
which is a standardized test of ambulation.
Data from the 48‑week Phase IIb study
showed that treated patients walked on
average 30 metres further than patients on
placebo. However, although the evaluation
© 2013 Macmillan Publishers Limited. All rights reserved
of dystrophin protein was included as an
exploratory endpoint, no correlation has
been reported between the 6MWT results
and the level of dystrophin expression.
Ataluren was generally well tolerated. In the
United States, all boys who participated in
the Phase IIb study have been in an exten‑
sion trial, and these are about to start in
other countries as well. It will be interesting
to determine whether there is a cumulative
effect of treatment, such that more signifi‑
cant clinical improvement will be seen at the
end of these extended trials.
Ataluren has demonstrated proof of prin‑
ciple of reading through stop codons as an
approach to therapy, although the efficacy
needs to be improved to achieve higher lev‑
els of dystrophin and improved clinical out‑
comes. Other compounds that show greater
efficacy are being reported but have yet to
be tested in patient trials19. This approach
is being applied to other genetic disorders,
such as cystic fibrosis and spinal muscular
atrophy (SMA), as well as for the treatment
of adenomatous polyposis coli-associated
colorectal cancers, where it would be
applicable to 24% of cases20.
Exon skipping
Approximately 83% of all DMD mutations3,
including most out‑of‑frame deletions, are
amenable to correction by the skipping of
specific exons21 (FIG. 2B). In this correction
strategy, RNaseH‑independent antisense
oligonucleotides (AONs) hybridize to
complementary sequences in or adjacent
to the target exon, modulating precursor
mRNA (pre-mRNA) splicing and achieving
reading frame restoration with the expres‑
sion of a BMD-like truncated dystrophin
protein. Proof of principle has been estab‑
lished in Phase I and Phase II clinical trials
led by groups in the Netherlands (Leiden
University Medical Centre in collaboration
with Prosensa–GlaxoSmithKline) and the
United Kingdom (MDEX Consortium in
collaboration with Sarepta Therapeutics),
targeting DMD exon 51, an approach
that is applicable to ~13% of patients. The
2′-O-methyl-phosphorothioate (2′OMe) and
morpholino phosphorodiamidate oligonu‑
cleotide (PMO) AONs used in these trials
were well-tolerated and restored dystrophin
protein to variable degrees (up to 55%
dystrophin-positive fibres in one patient)
when delivered via intramuscular 22,23 and
systemic routes24,25. Further clinical trials are
in progress to establish a long-term adminis‑
tration regimen, to evaluate clinical efficacy
in pivotal studies and to extend this to other
DMD exons.
 PROGRESS

A Rod domain
a Full-length dystrophin Actin binding H1 R R R H2 R R R R R R R R R R R R R R R R H3 R R R R R H4 CRD CTD
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

b ∆17–48 Actin binding H1 R R R R R R R R H4 CRD

H3 20 CTD
1 2 3 21 22 23 24
(BMD mutation)

∆D3990 Actin binding H1 R R R R R H4 CRD

1 2 H3 22 23 24
(Mini-dystrophin)

PTC
Rod domain
c Dystrophin-containing
nonsense mutation Actin binding H1 H2 H3 H4 CRD CTD

– Ataluren Shortened non-functional protein

mRNA
+ Ataluren

Rod domain
d Utrophin Actin binding H1 H2 H3 H4 CRD CTD

B U1 U2 SF2
snRNP snRNP U2 ASF
AF
a DMD 49 51 52
ESE ESS

U1 U2
snRNP AON snRNP U2
AF
b DMD and AON 49 51 52

49 52

Figure 2 | Dystrophin, utrophin and genetic approaches to therapy.  synthase (nNOS) to the sarcolemma, as is the case in some patients with
Aa | Wild-type dystrophin. Full-length dystrophin comprises an amino‑
terminal actin-binding domain, four hinge domains (H1–H4) and a rod
domain consisting of 24 spectrin-like repeats (R1–R24), within which lie
a second actin-binding domain, a cysteine-rich domain (CRD) and a
carboxy‑terminal domain (CTD). Ab | Mini-genes used in gene therapy. A
deletion of dystrophin exons 17–48 was identified in a mildly affected
patient with Becker’s muscular dystrophy (BMD) and was shown to correct
95% of the dystrophic pathology in the Mdx mouse. A clinical trial has been
carried out using mini-dystrophin ΔD3990, which consists of a truncated
protein that encodes the N‑terminal domain, the CRD and the rod domain,
but with a reduced number of spectrin repeats (namely, R1, R2, R22, R23
and R24) and three hinges (namely, H1, H3 and H4). Omitting the CTD was
not found to be crucial for function. Ac | Nonsense suppression. Ataluren
allows read-through of premature termination codons (PTC) to restore
production of a full-length functional dystrophin protein. Ad | Utrophin
lacks sequence corresponding to spectrin-like repeats 15 and 19 of dystro-
phin and binds actin only through the N‑terminal domain. Utrophin and
some of the dystrophin mini-genes will not localize neuronal nitric oxide
Nature
BMD. B | The principles of antisense oligonucleotide Reviews | Genetics
(AON)-mediated skip-
ping of dystrophin exon 51. Ba | The Duchenne muscular dystrophy (DMD)
locus in a patient with a deletion of exon 50. As a result of the deletion,
exons 49 and 51 are out‑of‑frame, which leads to an unstable precursor
mRNA (pre-mRNA) transcript and a lack of dystrophin protein. Also shown
in this region of the locus are some of the key cis- and trans-acting ele-
ments that regulate the splicing of the dystrophin pre-mRNA, including
U1 and U2 small nuclear RNAs (snRNAs), which define exon–intron bound-
aries and also exon internal sequences, such as exonic splicing enhancers
(ESEs) and exonic splicing silencers (ESSs) that promote and inhibit exon
inclusion during pre-mRNA splicing, respectively. Bb | An AON-targeting
exon internal sequences within exon 51 adjacent to putative ESE sites may
inhibit the association of splicing regulatory proteins (for example, of the
SF2 and ASF protein families) at this recognition site and therefore pro-
mote the skipping of this exon during pre-mRNA splicing. Skipping of exon
51 is able to restore a viable mRNA reading frame as axons 49 and 52 are
in‑frame exons, and therefore a truncated but semi-functional dystrophin
isoform is generated. snRNP, small nuclear ribonucleoprotein.

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Table 1 | Clinical trials using genetic therapies for Duchenne’s muscular dystrophy
Drug name Description Company Delivery Results to date Current Clinical trial number Refs
route stage and/or URL*
Viral gene therapy
Biostrophin rAAV2.5‑CMV Asklepios IM Failed to establish long-term Phase I http://www.askbio. 11
mini-dystrophin Biopharmaceutical (biceps) dystrophin expression; (completed) com
(d3990) immune response against
transgene in 4 out of 6 patients
Termination codon read-through
Ataluren Nonsense PTC Therapeutics Oral Slowed loss of walking ability Phase III NCT01557400; http:// 17,
suppression in patients with DMD or BMD www.ptcbio.com 49
(n = 174) at the lower of two
doses tested
Exon skipping
Eteplirsen PMO morpholino Sarepta IV Well-tolerated and restored Phase II NCT00844597; 22,
(AVI‑4568) targeting exon 51 Therapeutics dystrophin expression in http://www. 24
7 out of 19 patients in a sareptatherapeutics.
dose-dependent manner com
(<20% normal levels)
GSK2402968 2′OMePS AON Prosensa– SC Restored dystrophin Phase III NCT01480245; 23,
(PRO051); targeting exon 51 GlaxoSmithKline expression in 10 out of 12 http://www.gsk.com; 25
Drisapersen patients (<20% normal levels) http://www.prosensa.
eu
PRO044 2′OMePS AON Prosensa SC or IV Study ongoing Phase I/IIa NCT01037309 50
targeting exon 44
Increasing levels of utrophin
SMT‑C1100 Utrophin Summit PLC Oral Safe, well-tolerated, achieved Phase I http://www. 42
modulator plasma levels shown to (completed) summitplc.com
increase utrophin in DMD
patient cells in vitro
*Where possible, the clinical trial identification number is given where the trial is ongoing or where data have not yet been published. 2′OMePS, 2′O‑methyl-
phosphorothioate; AAV, adeno-associated virus; AON, antisense oligonucleotide. BMD, Becker muscular dystrophy; CMV, cytomegalovirus; DMD, Duchenne
muscular dystrophy; IM, intramuscular; IV, intravenous; PMO, phosphorodiamidate morpholino oligomer; SC, subcutaneous.

Although progress is promising, the
translation of exon-skipping therapies is
complex, and caution in the interpretation
of current clinical trial data is warranted.
First, the efficacy of exon-skipping AONs is
limited by poor cellular uptake, resulting in
low and variable levels of dystrophin protein
restoration in skeletal muscle and little or
no restoration in heart muscle. A potential
solution is the development of second-
generation AONs with improved skeletal
and cardiac muscle penetration26. Second,
the variable nature of the disease course and
of the current clinical outcome measures
necessitates that clinical trials are appropri‑
ately powered and double-blind and that the
AON drug is evaluated against a placebo or
a reference DMD natural history data set.
These are demanding requirements for a
rare disease but are nonetheless important.
The most likely outcome with first-
generation exon-skipping AONs is limited
clinical efficacy. This constitutes progress,
but the level of efficacy would probably
fall short of what is required for a disease-
modifying therapy. However, a number of
factors might improve outcome in certain
cases. From initial clinical trials, it appears
that some patients might be ‘high responders’,
although whether this has a genetic or
stochastic basis is unknown24. Some muta‑
tions might be better targets for therapy as
some DMD exons appear easier to skip27.
Finally, prolonged treatment might improve
clinical outcome as may be the case with
read-through of stop codons.
However, further important caveats exist
regarding the exon-skipping approach.
These include, first, that the restored
dystrophin protein is truncated and semi-
functional, and therefore at best the clinical
outcome is conversion to the corresponding
BMD phenotype. Second, therapy is highly
personalized and mutation-specific, neces‑
sitating the clinical development of multiple
AONs. Moreover, this mutation-specific
requirement has direct cost and regula‑
tory implications, given that each AON in
development is regarded by the US Food
and Drug Administration (FDA) and other
regulatory agencies as a new drug. Third,
the fact that therapy is highly personalized
implies that high-frequency mutations will
be addressed first and that some patients
with DMD who harbour lower-frequency
mutations might remain untreated. These
problems could be partially solved with
the advent of successful multi-exon skip‑
ping, which has recently been demonstrated
in principle28. An additional issue is that
although first-generation AONs have
acceptable safety profiles, long-term safety
is currently unknown, and this is crucial
when treatment is essentially life-long. More
generally, the lack of validated biomarkers to
monitor AON efficacy continues to hinder
DMD drug development, although
candidate serum protein and microRNA
biomarkers have now been identified29–31.
Overall, although results targeting exon
51 are promising, major hurdles in the clini‑
cal development of exon-skipping AONs
remain that are likely to limit the effective‑
ness of first-generation compounds. To
maximize the likelihood of success, efforts
should focus on validating appropriate bio‑
markers, understanding factors related to
individual responses to exon-skipping AON

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© 2013 Macmillan Publishers Limited. All rights reserved


compounds, advancing second-generation
AONs and establishing an accelerated regu‑
latory process. Although success to date is
partial, the progress already made is having
an impact on the development of AON-
based therapies for related neuromuscular
disorders, including SMA and myotonic
dystrophy 21. Beyond such diseases, the use of
AONs to modulate pre-mRNA splicing has
also been successfully extended to cancer, in
which disrupted alternative splicing com‑
monly occurs and in which redirecting splic‑
ing of, for example, signal transducer and
activator of transcription 3 (STAT3) can lead
to a favourable anti-oncogenic outcome32.
Increasing levels of utrophin
The dystrophin-related protein utrophin
shows sequence and structural similarity
to dystrophin and can functionally com‑
pensate for the lack of dystrophin in the
mdx mouse4,33,34. Utrophin is restricted to
neuromuscular and myotendinous junc‑
tions in adult muscle, but during embryonic
development and in patients with DMD, it
is localized at the sarcolemma when dystro‑
phin is absent or present only at low levels.
Studies in animal models have provided
compelling evidence that utrophin func‑
tions in these scenarios directly to protect
the muscle against dystrophic degeneration.
However, utrophin does not anchor nNOS to
the sarcolemma, which is a requirement
to regulate blood flow to the muscle and to
ensure that all of its metabolic needs are
met. This issue may also be encountered in
strategies that are based on the skipping of
particular exons and for some mini-genes.
The implications of this are uncertain, given
that there may be compensatory pathways
for the lack of nNOS and that several mildly
affected patients with BMD have large dele‑
tions that also lack nNOS binding sites9,35,36.
In the mdx mouse, an increase in utrophin
protein in all tissues, which is sufficient
for complete rescue, does not cause
toxicity 37. Encouragingly, small differences
in utrophin protein levels between patients
with DMD positively correlate with the age
of confinement to a wheelchair, demon‑
strating that even small increases might be
beneficial38.
Utrophin levels can be increased by
direct delivery of the protein39, by stabi‑
lization of the protein or RNA40,41 or by
transcriptional upregulation42. Agents such
as biglycan that stabilize the DAPC hold
therapeutic promise, and clinical trials
are planned43, but whether this approach
will result in sufficient utrophin levels for
therapeutic benefit remains unknown.
NATURE REVIEWS | GENETICS VOLUME 14 | JUNE 2013 | 377
Utrophin is more highly expressed in slow
fibres, and therefore the promotion of the
slow oxidative myogenic programme may
be beneficial. This has been demonstrated
through the activation of the calcineurin–
NFAT (nuclear factor of activated T cells)
pathway 44 and by increasing peroxisome
proliferator-activated receptor‑γ coactivator
1α (PGC1α)45. However, PGC1α regulates
the neuromuscular junction programme and
therefore may be affecting other pathways
in addition to increasing utrophin levels.
Other pharmacological activators of oxida‑
tive metabolism may also be helpful, and
some are in clinical trials for other disorders,
such as diabetes4. Summit plc has recently
reported positive data from a Phase I trial of
SMT C1100, which is a drug derived from
a high-throughput transcription screen and
which increases utrophin RNA and protein
up to twofold in some muscles42. This is now
proceeding to Phase II. It is worth noting
that, in the wild-type mouse, very high levels
of utrophin are observed in the kidneys and
lungs, suggesting that high levels are possible
in adult tissue.
Increasing utrophin should be effective in
all patients with DMD, irrespective of their
dystrophin mutation and will circumvent
immunological challenges faced by
dystrophin-based therapies13. Although none
of the utrophin-based approaches developed
so far has achieved the two- to fourfold
increase that has been set as the benchmark
for preclinical rescue46, the continued clinical
evaluation of SMT C1100 may provide the
first insight into therapeutic levels required
in patients. A recent study has reported in
the mdx mouse that as little as 4% of wild-
type dystrophin levels may be sufficient
for significant survival and motor function
improvement, emphasizing the need to take
drugs such as SMT C1100 into patients for
evaluation47. The change of expression of a
related or similar protein was first used for
the treatment of β‑thalassaemia, in which
increased levels of fetal haemoglobin were
used to compensate for the lack of the adult
β-globin gene48. Such an approach could be
applicable to many other disorders.
Conclusion
Five years ago, effective treatment for DMD
seemed an impossible dream, and few phar‑
maceutical companies were interested in
investing in therapy for a fairly rare orphan
disease. However, this has all changed, as
DMD is now seen as a model for the devel‑
opment of treatment on the basis of the
specific mutation or mutations that are pre‑
sent in an individual (that is, personalized
© 2013 Macmillan Publishers Limited. All rights reserved
PROGRESS
medicine), and advances in technology have
made many of the problems with therapeutic
approaches more tractable. Many challenges
remain, however, not least for the develop‑
ment of reliable endpoints for clinical trials
in view of the variability in the 6MWT. The
problem of delivery to all muscles of the
body will also need to be resolved. However,
there is little doubt that although a cure
remains some way off, treatments are cur‑
rently entering trials that have the potential
for providing a significant clinical impact on
the quality of life of patients. In turn, these
approaches are being applied to many other
genetic disorders. The age of genomic medi‑
cine is moving forwards with rapid speed.
Rebecca J. Fairclough, Matthew J. Wood and Kay
E. Davies are at the Department of Physiology,
Anatomy and Genetics, University of Oxford, Parks
Road, Oxford OX1 3PT, UK.
Rebeccan J. Fairclough and Kay E. Davies are also at
the MRC Functional Genomics Unit, MRC Functional
Genomics Unit, Department of Physiology, Anatomy
and Genetics, Parks Road, Oxford OX1 3PT, UK.
Correspondence to K.E.D. 
e-mail: kay.davies@dpag.ox.ac.uk
doi:10.1038/nrg3460
Published online 23 April 2013
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Acknowledgements
The authors are very grateful to the UK Medical Research
Council, the Wellcome Trust, the UK Muscular Dystrophy
Campaign, the US Muscular Dystrophy Association, Action
Duchenne, the Association Française Contre les Myopathies
and the International Consortium on Exon Skipping for
support.
Competing interests statement
The authors declare competing financial interests: see Web
version for details.
FURTHER INFORMATION
Matthew Wood’s homepage: http://www.dpag.ox.ac.uk/
academic_staff/matthew_wood
MRC Functional Genomics Unit homepage: http://www.
mrcfgu.ox.ac.uk
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