Induced pluripotent stem cells as a model To test gene augmentation therapy for Choroideremia

Vasireddy, Vidyullatha, Mills, Jason A., Gaddameedi, Rajashekhar, Basner-Tschakarjan, Etiena, Kohnke, Monica, Black, Aaron H., Alexandrov, Kirill, Maguire, Albert M., Chung, Daniel, Mac, Helen, Sullivan, Lisa, Gadue, Paul, Bennicelli, Jeannette L., French, Deborah L. and Bennett, Jean (2013). Induced pluripotent stem cells as a model To test gene augmentation therapy for Choroideremia. In: ASGCT 16th Annual Meeting. 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT), Salt Lake City, UT, United States, (S87-S87). 15-18 May 2013.

Author Vasireddy, Vidyullatha
Mills, Jason A.
Gaddameedi, Rajashekhar
Basner-Tschakarjan, Etiena
Kohnke, Monica
Black, Aaron H.
Alexandrov, Kirill
Maguire, Albert M.
Chung, Daniel
Mac, Helen
Sullivan, Lisa
Gadue, Paul
Bennicelli, Jeannette L.
French, Deborah L.
Bennett, Jean
Title of paper Induced pluripotent stem cells as a model To test gene augmentation therapy for Choroideremia
Conference name 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT)
Conference location Salt Lake City, UT, United States
Conference dates 15-18 May 2013
Proceedings title ASGCT 16th Annual Meeting   Check publisher's open access policy
Journal name Molecular Therapy   Check publisher's open access policy
Place of Publication London, United Kingdom
Publisher Nature Publishing Group
Publication Year 2013
Year available 2013
Sub-type Published abstract
ISSN 1525-0016
Volume 21
Issue Supp. 1
Start page S87
End page S87
Total pages 1
Collection year 2014
Language eng
Abstract/Summary Choroideremia (CHM) is an X-linked, blinding, inherited retinal degeneration that is symptomatic in childhood and leads to total blindness in midlife. The disease is characterized by the degeneration of photoreceptors, retinal pigment epithelium (RPE) and choriocapillaris. The causative factor for CHM was identifi ed as a defect in the Rab Escort Protein 1 (REP1) which is involved in prenylation of Rab proteins. The nature and onset of the disease and the size of the gene makes CHM an excellent target for recombinant adeno-associated virus (rAAV) mediated gene therapy. However, the animal model of this disease is not an exact replica of the condition and is not readily available. Therefore, we generated and evaluated induced pluripotent stems cells (iPSCs) from CHM subjects as in vitro models to explore the potential of gene augmentation therapy. A recombinant adeno-associated virus (AAV2) was generated that delivers the wild-type human CHM cDNA driven by a constitutive promoter. Infection of iPSCs with AAV2-CHM resulted in the expression of the CHM protein and rescue of enzymatic function in the defective cells. The gene transfer is effi cient and appears to be safe in the short-term, as shown by studies in affected cells and in normalsighted animal models. These studies not only aid in deciphering the pathogenetic mechanisms of the disease, but also pave the way for a human gene therapy clinical trial for CHM.
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Conference Paper
Collection: Institute for Molecular Bioscience - Publications
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