ESR11: ABCA4 knockout pig as model for gene therapy in STGD1
Abstract
Abca4-/- knockout mice are currently used as animal models of STGD1, but they recapitulate only some of the features of the disease, which might be due to the structure of the mouse retina, which largely differs from that of humans. The absence of an appropriate animal model severely limits both the understanding of STGD1 mechanisms as well as the testing of novel potential therapeutic strategies. Among non-primate mammals, the porcine eye shares many similarities with the human retina including anatomy, size, and a high cone/rod ratio. In addition, unlike in non-human primates or other large species, pig transgenesis is particularly advanced. ESR11 will generate a pig model of STGD1, by exploring either nuclear transfer from fibroblasts which have been genetically modified using TALEN technology in embryonic stem cells, or photoreceptor somatic gene transfer of CRISPR/Cas9 with adeno-associated viral vectors. The generation of in vivo models of STGD1 will provide unique tools for both studying the mechanism of STGD1 rod and cone cell death as well as testing new therapies including gene therapy approaches recently developed by us.
Partner
Telethon Institute of Genetics and Medicine, Naples, Italy (www.telethon.it; www.tigem.it)
Supervisor
Prof. Dr. A. Auricchio
Abca4-/- knockout mice are currently used as animal models of STGD1, but they recapitulate only some of the features of the disease, which might be due to the structure of the mouse retina, which largely differs from that of humans. The absence of an appropriate animal model severely limits both the understanding of STGD1 mechanisms as well as the testing of novel potential therapeutic strategies. Among non-primate mammals, the porcine eye shares many similarities with the human retina including anatomy, size, and a high cone/rod ratio. In addition, unlike in non-human primates or other large species, pig transgenesis is particularly advanced. ESR11 will generate a pig model of STGD1, by exploring either nuclear transfer from fibroblasts which have been genetically modified using TALEN technology in embryonic stem cells, or photoreceptor somatic gene transfer of CRISPR/Cas9 with adeno-associated viral vectors. The generation of in vivo models of STGD1 will provide unique tools for both studying the mechanism of STGD1 rod and cone cell death as well as testing new therapies including gene therapy approaches recently developed by us.
Partner
Telethon Institute of Genetics and Medicine, Naples, Italy (www.telethon.it; www.tigem.it)
Supervisor
Prof. Dr. A. Auricchio
