TY - JOUR
T1 - Towards germline gene therapy of inherited mitochondrial diseases
AU - Tachibana, Masahito
AU - Amato, Paula
AU - Sparman, Michelle
AU - Woodward, Joy
AU - Sanchis, Dario Melguizo
AU - Ma, Hong
AU - Gutierrez, Nuria Marti
AU - Tippner-Hedges, Rebecca
AU - Kang, Eunju
AU - Lee, Hyo Sang
AU - Ramsey, Cathy
AU - Masterson, Keith
AU - Battaglia, David
AU - Lee, David
AU - Wu, Diana
AU - Jensen, Jeffrey
AU - Patton, Phillip
AU - Gokhale, Sumita
AU - Stouffer, Richard
AU - Mitalipov, Shoukhrat
PY - 2013/2/7
Y1 - 2013/2/7
N2 - Mutations in mitochondrial DNA (mtDNA) are associated with severe human diseases and are maternally inherited through the egg's cytoplasm. Here we investigated the feasibility of mtDNA replacement in human oocytes by spindle transfer (ST; also called spindle-chromosomal complex transfer). Of 106 human oocytes donated for research, 65 were subjected to reciprocal ST and 33 served as controls. Fertilization rate in ST oocytes (73%) was similar to controls (75%); however, a significant portion of ST zygotes (52%) showed abnormal fertilization as determined by an irregular number of pronuclei. Among normally fertilized ST zygotes, blastocyst development (62%) and embryonic stem cell isolation (38%) rates were comparable to controls. All embryonic stem cell lines derived from ST zygotes had normal euploid karyotypes and contained exclusively donor mtDNA. The mtDNA can be efficiently replaced in human oocytes. Although some ST oocytes displayed abnormal fertilization, remaining embryos were capable of developing to blastocysts and producing embryonic stem cells similar to controls.
AB - Mutations in mitochondrial DNA (mtDNA) are associated with severe human diseases and are maternally inherited through the egg's cytoplasm. Here we investigated the feasibility of mtDNA replacement in human oocytes by spindle transfer (ST; also called spindle-chromosomal complex transfer). Of 106 human oocytes donated for research, 65 were subjected to reciprocal ST and 33 served as controls. Fertilization rate in ST oocytes (73%) was similar to controls (75%); however, a significant portion of ST zygotes (52%) showed abnormal fertilization as determined by an irregular number of pronuclei. Among normally fertilized ST zygotes, blastocyst development (62%) and embryonic stem cell isolation (38%) rates were comparable to controls. All embryonic stem cell lines derived from ST zygotes had normal euploid karyotypes and contained exclusively donor mtDNA. The mtDNA can be efficiently replaced in human oocytes. Although some ST oocytes displayed abnormal fertilization, remaining embryos were capable of developing to blastocysts and producing embryonic stem cells similar to controls.
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UR - http://www.scopus.com/inward/citedby.url?scp=84873618709&partnerID=8YFLogxK
M3 - Article
SN - 0028-0836
VL - 494
SP - 627
EP - 631
JO - Nature
JF - Nature
IS - 7435
ER -