The Experts below are selected from a list of 996 Experts worldwide ranked by ideXlab platform
David G. Capco - One of the best experts on this subject based on the ideXlab platform.
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CRISPR/Cas9 and Mitochondrial gene Replacement Therapy: promising techniques and ethical considerations.
American journal of stem cells, 2016Co-Authors: Sarah Fogleman, Casey Santana, Casey Bishop, Alyssa M. Miller, David G. CapcoAbstract:Thousands of mothers are at risk of transmitting Mitochondrial diseases to their offspring each year, with the most severe form of these diseases being fatal [1]. With no cure, transmission prevention is the only current hope for decreasing the disease incidence. Current methods of prevention rely on low mutant maternal Mitochondrial DNA levels, while those with levels close to or above threshold (>60%) are still at a very high risk of transmission [2]. Two novel approaches may offer hope for preventing and treating Mitochondrial disease: Mitochondrial Replacement Therapy, and CRISPR/Cas9. Mitochondrial Replacement Therapy has emerged as a promising tool that has the potential to prevent transmission in patients with higher mutant Mitochondrial loads. This method is the subject of many ethical concerns due its use of a donor embryo to transplant the patient's nuclear DNA; however, it has ultimately been approved for use in the United Kingdom and was recently declared ethically permissible by the FDA. The leading-edge CRISPR/Cas9 technology exploits the principles of bacterial immune function to target and remove specific sequences of mutated DNA. This may have potential in treating individuals with disease caused by mutant Mitochondrial DNA. As the technology progresses, it is important that the ethical considerations herein emerge and become more established. The purpose of this review is to discuss current research surrounding the procedure and efficacy of the techniques, compare the ethical concerns of each approach, and look into the future of Mitochondrial gene Replacement Therapy.
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crispr cas9 and Mitochondrial gene Replacement Therapy promising techniques and ethical considerations
Journal of stem cells, 2016Co-Authors: Sarah Fogleman, Casey Santana, Casey Bishop, Alyssa Miller, David G. CapcoAbstract:Thousands of mothers are at risk of transmitting Mitochondrial diseases to their offspring each year, with the most severe form of these diseases being fatal [1]. With no cure, transmission prevention is the only current hope for decreasing the disease incidence. Current methods of prevention rely on low mutant maternal Mitochondrial DNA levels, while those with levels close to or above threshold (>60%) are still at a very high risk of transmission [2]. Two novel approaches may offer hope for preventing and treating Mitochondrial disease: Mitochondrial Replacement Therapy, and CRISPR/Cas9. Mitochondrial Replacement Therapy has emerged as a promising tool that has the potential to prevent transmission in patients with higher mutant Mitochondrial loads. This method is the subject of many ethical concerns due its use of a donor embryo to transplant the patient's nuclear DNA; however, it has ultimately been approved for use in the United Kingdom and was recently declared ethically permissible by the FDA. The leading-edge CRISPR/Cas9 technology exploits the principles of bacterial immune function to target and remove specific sequences of mutated DNA. This may have potential in treating individuals with disease caused by mutant Mitochondrial DNA. As the technology progresses, it is important that the ethical considerations herein emerge and become more established. The purpose of this review is to discuss current research surrounding the procedure and efficacy of the techniques, compare the ethical concerns of each approach, and look into the future of Mitochondrial gene Replacement Therapy.
Ryan C Oneil - One of the best experts on this subject based on the ideXlab platform.
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functional human oocytes generated by transfer of polar body genomes
Cell Stem Cell, 2017Co-Authors: Manoj Hariharan, Ryan C Oneil, Nuria Marti Gutierrez, Zhuzhu Z Zhang, Refik Kayali, Cengiz Cinnioglu, Yupeng He, Eunju KangAbstract:Summary Oocyte defects lie at the heart of some forms of infertility and could potentially be addressed therapeutically by alternative routes for oocyte formation. Here, we describe the generation of functional human oocytes following nuclear transfer of first polar body (PB1) genomes from metaphase II (MII) oocytes into enucleated donor MII cytoplasm (PBNT). The reconstructed oocytes supported the formation of de novo meiotic spindles and, after fertilization with sperm, meiosis completion and formation of normal diploid zygotes. While PBNT zygotes developed to blastocysts less frequently (42%) than controls (75%), genome-wide genetic, epigenetic, and transcriptional analyses of PBNT and control ESCs indicated comparable numbers of structural variations and markedly similar DNA methylation and transcriptome profiles. We conclude that rescue of PB1 genetic material via introduction into donor cytoplasm may offer a source of oocytes for infertility treatment or Mitochondrial Replacement Therapy for mtDNA disease.
Qi Zhang - One of the best experts on this subject based on the ideXlab platform.
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towards clinical application of pronuclear transfer to prevent Mitochondrial dna disease
Nature, 2016Co-Authors: Louise Hyslop, Paul Blakeley, Lyndsey Craven, Jessica Richardson, N M Fogarty, E Fragouli, Mahdi Lamb, Sissy E Wamaitha, Nilendran Prathalingam, Qi ZhangAbstract:Preclinical evaluation and optimization of Mitochondrial Replacement Therapy reveals that a modified form of pronuclear transfer is likely to give rise to normal pregnancies with a reduced risk of Mitochondrial DNA disease, but may need further modification to eradicate the disease in all cases. These authors report a preclinical evaluation and optimization of mitochondria Replacement Therapy using pronuclear transfer. The influence of different parameters and manipulations is evaluated in normally fertilized human embryos, and the improved protocol is shown to produce blastocysts with a low level of Mitochondrial carryover. The results highlight the need for continued optimization and monitoring of mitochondria Replacement Therapy techniques for future human application. Mitochondrial DNA (mtDNA) mutations are maternally inherited and are associated with a broad range of debilitating and fatal diseases1. Reproductive technologies designed to uncouple the inheritance of mtDNA from nuclear DNA may enable affected women to have a genetically related child with a greatly reduced risk of mtDNA disease. Here we report the first preclinical studies on pronuclear transplantation (PNT). Surprisingly, techniques used in proof-of-concept studies involving abnormally fertilized human zygotes2 were not well tolerated by normally fertilized zygotes. We have therefore developed an alternative approach based on transplanting pronuclei shortly after completion of meiosis rather than shortly before the first mitotic division. This promotes efficient development to the blastocyst stage with no detectable effect on aneuploidy or gene expression. After optimization, mtDNA carryover was reduced to <2% in the majority (79%) of PNT blastocysts. The importance of reducing carryover to the lowest possible levels is highlighted by a progressive increase in heteroplasmy in a stem cell line derived from a PNT blastocyst with 4% mtDNA carryover. We conclude that PNT has the potential to reduce the risk of mtDNA disease, but it may not guarantee prevention.
Eunju Kang - One of the best experts on this subject based on the ideXlab platform.
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functional human oocytes generated by transfer of polar body genomes
Cell Stem Cell, 2017Co-Authors: Manoj Hariharan, Ryan C Oneil, Nuria Marti Gutierrez, Zhuzhu Z Zhang, Refik Kayali, Cengiz Cinnioglu, Yupeng He, Eunju KangAbstract:Summary Oocyte defects lie at the heart of some forms of infertility and could potentially be addressed therapeutically by alternative routes for oocyte formation. Here, we describe the generation of functional human oocytes following nuclear transfer of first polar body (PB1) genomes from metaphase II (MII) oocytes into enucleated donor MII cytoplasm (PBNT). The reconstructed oocytes supported the formation of de novo meiotic spindles and, after fertilization with sperm, meiosis completion and formation of normal diploid zygotes. While PBNT zygotes developed to blastocysts less frequently (42%) than controls (75%), genome-wide genetic, epigenetic, and transcriptional analyses of PBNT and control ESCs indicated comparable numbers of structural variations and markedly similar DNA methylation and transcriptome profiles. We conclude that rescue of PB1 genetic material via introduction into donor cytoplasm may offer a source of oocytes for infertility treatment or Mitochondrial Replacement Therapy for mtDNA disease.
Sarah Fogleman - One of the best experts on this subject based on the ideXlab platform.
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CRISPR/Cas9 and Mitochondrial gene Replacement Therapy: promising techniques and ethical considerations.
American journal of stem cells, 2016Co-Authors: Sarah Fogleman, Casey Santana, Casey Bishop, Alyssa M. Miller, David G. CapcoAbstract:Thousands of mothers are at risk of transmitting Mitochondrial diseases to their offspring each year, with the most severe form of these diseases being fatal [1]. With no cure, transmission prevention is the only current hope for decreasing the disease incidence. Current methods of prevention rely on low mutant maternal Mitochondrial DNA levels, while those with levels close to or above threshold (>60%) are still at a very high risk of transmission [2]. Two novel approaches may offer hope for preventing and treating Mitochondrial disease: Mitochondrial Replacement Therapy, and CRISPR/Cas9. Mitochondrial Replacement Therapy has emerged as a promising tool that has the potential to prevent transmission in patients with higher mutant Mitochondrial loads. This method is the subject of many ethical concerns due its use of a donor embryo to transplant the patient's nuclear DNA; however, it has ultimately been approved for use in the United Kingdom and was recently declared ethically permissible by the FDA. The leading-edge CRISPR/Cas9 technology exploits the principles of bacterial immune function to target and remove specific sequences of mutated DNA. This may have potential in treating individuals with disease caused by mutant Mitochondrial DNA. As the technology progresses, it is important that the ethical considerations herein emerge and become more established. The purpose of this review is to discuss current research surrounding the procedure and efficacy of the techniques, compare the ethical concerns of each approach, and look into the future of Mitochondrial gene Replacement Therapy.
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crispr cas9 and Mitochondrial gene Replacement Therapy promising techniques and ethical considerations
Journal of stem cells, 2016Co-Authors: Sarah Fogleman, Casey Santana, Casey Bishop, Alyssa Miller, David G. CapcoAbstract:Thousands of mothers are at risk of transmitting Mitochondrial diseases to their offspring each year, with the most severe form of these diseases being fatal [1]. With no cure, transmission prevention is the only current hope for decreasing the disease incidence. Current methods of prevention rely on low mutant maternal Mitochondrial DNA levels, while those with levels close to or above threshold (>60%) are still at a very high risk of transmission [2]. Two novel approaches may offer hope for preventing and treating Mitochondrial disease: Mitochondrial Replacement Therapy, and CRISPR/Cas9. Mitochondrial Replacement Therapy has emerged as a promising tool that has the potential to prevent transmission in patients with higher mutant Mitochondrial loads. This method is the subject of many ethical concerns due its use of a donor embryo to transplant the patient's nuclear DNA; however, it has ultimately been approved for use in the United Kingdom and was recently declared ethically permissible by the FDA. The leading-edge CRISPR/Cas9 technology exploits the principles of bacterial immune function to target and remove specific sequences of mutated DNA. This may have potential in treating individuals with disease caused by mutant Mitochondrial DNA. As the technology progresses, it is important that the ethical considerations herein emerge and become more established. The purpose of this review is to discuss current research surrounding the procedure and efficacy of the techniques, compare the ethical concerns of each approach, and look into the future of Mitochondrial gene Replacement Therapy.