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conferenceseries.com
October 26-27, 2016 Chicago, USA
Annual Congress on
Rare Diseases & Orphan Drugs
Volume 7, Issue 5 (Suppl) J Genet Syndr Gene Ther
ISSN: 2157-7412 JGSGT, an open access journal Rare Diseases 2016
October 26-27, 2016
Potential treatments for rare diseases: Cell therapy, gene therapy and genome editing
Jacques P Tremblay
Laval University, Canada
All hereditary diseases are due to modification in the patient genome insertion, deletion or modification of one or several
nucleotides among the 6 billion nucleotides of the human genome. Several potential therapeutic approaches to treat these
hereditary diseases have been developed over the years. For some recessive diseases the transplantation of allogenic cells obtained
from a healthy donor can permit to deliver the normal gene to compensate for the mutated gene. This approach is under clinical
trial for Duchenne Muscular Dystrophy. A compensatory normal gene to treat a recessive hereditary disease may also be introduced
in the patient own cells in culture or directly in vivo by using viral vectors. The Adeno Associated Viruses (AAV), are currently the
vectors of choice for such a therapeutic approaches. Various specific nucleases (meganucleases, Zinc Finger Nucleases, TALENs and
the CRISPR/Cas9 system) have been investigated during the lasts 10 years and now permit to precisely correct a gene responsible for a
hereditary disease. This type of approaches is the only one that can be used for dominant diseases. This approach may also be used to
correct large genes, which are too big to be delivered by AAV. My team and several others have already used this approach to correct
the dystrophin gene, as a treatment for Duchenne Muscular Dystrophy. Indeed by using these specific nucleases, it is possible to
induce double strands breaks in the dystrophin gene to restore the normal reading frame by micro-insertions, micro-deletions or by
deleting complete exons or parts of exons. My team is also attempting to restore a completely normal dystrophin protein by inserting
the exons, which are missing in the patient genome. My team has also been able to remove with the CRISPR/Cas9 system the long
trinucleotide repeat in intron 1 of the frataxin gene responsible for Friedreich ataxia and thus increase the expression of frataxin in
patient cells. The TALE proteins and a defective Cas9 nuclease (dCas9) may also be fused with a transcription activation domain, such
as VP64, to target a gene promoter to increase specifically the expression of that gene. My team has successfully used that approach in
cells of Friedreich patients. The CRISPR/Cas9 technology may also be used to correct a gene by a process called homology directed
repair. This technique permits to modify one or several nucleotides in the whole human genome. Thus the progress in cell therapy,
gene therapy and genome editing permits to dream of developing therapies for all hereditary diseases over the coming years. The
main limiting factor is the financial support for this type of research.
Biography
Jacques P Tremblay has completed his PhD in Neurosciences in 1974 at University of California at San Diego. He has published 261 articles in peer-reviewed
journals and has been serving as Deputy Editor of Molecular Therapy and Cell Transplantation. His laboratory is currently working on cell and gene therapies for
Duchenne muscular dystrophy, Friedreich ataxia and Alzheimer disease.
Jacques P Tremblay, J Genet Syndr Gene Ther 2016, 7:5 (Suppl)