Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Optimized lentiviral vector for restoration of full-length dystrophin via a cell-mediated approach in a mouse model of Duchenne muscular dystrophy
  • Publication Type:
    Journal article
  • Authors:
    Meng J, Moore M, Counsell J, Muntoni F, Popplewell L, Morgan J
  • Publisher:
    Elsevier BV
  • Publication date:
  • Journal:
    Molecular Therapy: Methods & Clinical Development
  • Status:
  • Language:
  • Notes:
    Copyright © 2022 The Author(s). This is an Open Access article published under a Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/).
Duchenne muscular dystrophy (DMD) is a muscle wasting disorder caused by mutations in the DMD gene. Restoration of full-length dystrophin protein in skeletal muscle would have therapeutic benefit, but lentivirally-mediated delivery of such a large gene in vivo has been hindered by lack of tissue-specificity, limited transduction and insufficient transgene expression. To address these problems, we developed a lentiviral vector, which contained a muscle-specific promoter and sequence optimized full-length dystrophin, to constrain the dystrophin expression to differentiated myotubes/myofibres and enhance the transgene expression. We further explored the efficiency of restoration of full-length dystrophin in vivo, by grafting DMD myoblasts that had been corrected by this optimized lentiviral vector intramuscularly into an immunodeficient DMD mouse model. We showed that these lentivirally-corrected DMD myoblasts effectively reconstituted full-length dystrophin expression in 93.58±2.17% of the myotubes in vitro. Moreover, dystrophin was restored in 64.4±2.87% of the donor-derived regenerated muscle fibres in vivo, which was able to recruit members of the dystrophin glycoprotein complex at the sarcolemma. This study represents a significant advance over existing cell-mediated gene therapy strategies for DMD that aim to restore full-length dystrophin expression in skeletal muscle.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers Show More
Department of Targeted Intervention
Genetics & Genomic Medicine Dept
Developmental Neurosciences Dept
Developmental Neurosciences Dept
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by