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Publication Detail
High-efficiency transduction of spinal cord motor neurons by intrauterine delivery of integration-deficient lentiviral vectors.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Ahmed SG, Waddington SN, Boza-Morán MG, Yáñez-Muñoz RJ
  • Publication date:
    28/12/2017
  • Journal:
    Journal of controlled release : official journal of the Controlled Release Society
  • Medium:
    Print-Electronic
  • Status:
    Published
  • Print ISSN:
    0168-3659
  • Language:
    eng
  • Addresses:
    AGCTlab.org, Centre for Biomedical Sciences, School of Biological Sciences, Royal Holloway, University of London, Egham TW20 0EX, UK; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Egypt.
Abstract
Integration-deficient lentiviral vectors (IDLVs) are promising gene delivery tools that retain the high transduction efficiency of standard lentiviral vectors, yet fail to integrate as proviruses and are instead converted into episomal circles. These episomes are metabolically stable and support long-term expression of transgenes in non-dividing cells, exhibiting a decreased risk of insertional mutagenesis. We have embarked on an extensive study to compare the transduction efficiency of IDLVs pseudotyped with different envelopes (vesicular stomatitis, Rabies, Mokola and Ross River viral envelopes) and self-complementary adeno-associated viral vectors, serotype-9 (scAAV-9) in spinal cord tissues after intraspinal injection of mouse embryos (E16). Our results indicate that IDLVs can transduce motor neurons (MNs) at extremely high efficiency regardless of the envelope pseudotype while scAAV9 mediates gene delivery to ~40% of spinal cord motor neurons, with other non-neuronal cells also transduced. Long-term expression studies revealed stable gene expression at 7months post-injection. Taken together, the results of this study indicate that IDLVs may be efficient tools for in utero cord transduction in therapeutic strategies such as for treatment of inherited early childhood neurodegenerative diseases.
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