美國全國兒童醫(yī)院的研究者公布了一份基因治療方案,，改善鼠實驗中的遺傳性血液紊亂-β-地中海貧血病癥,，基因改善是使用鼠的未受精卵制造胚胎干細胞系,。這些干細胞系沒有遺傳疾病基因,，可用于小鼠的移植治療,。
該發(fā)現(xiàn)發(fā)布在《臨床研究期刊》(Journal of Clinical Investigation)上,，對于治療常染色體顯性遺傳疾病,，如β-地中海貧血,、結節(jié)性硬化癥或亨廷頓氏病的治療方案提供了新的希望。
胚胎干細胞可發(fā)展成各種類型的細胞,，可用于許多疾病的治療,。未受精卵可被培養(yǎng)成胚胎干細胞，即孤雌胚胎干細胞,。全國兒童醫(yī)院研究所分子與人類遺傳學中心的首席研究員,，麥克考林博士認為：孤雌胚胎干細胞可以分化為各種組織類型，正如干細胞是來自于受精的胚胎,。在此之前,，該研究組表示來自于孤雌胚胎細胞的血液細胞可在小鼠體內提供健康,、長期的血液置換。
麥克考林博士說,，孤雌干細胞的優(yōu)點不僅是不需要受精,，并且接受者的免疫系統(tǒng)不會將其作為異物，減少排斥反應的問題,。此外,，由于孤雌胚胎干細胞是來自于生殖細胞-包含了單一的基因信息，他們不會有某種畸變基因的存在,。
麥克考林博士與來自賓夕法尼亞大學,、北卡羅來納州大學和明尼蘇達大學的同事們共同驗證了孤雌胚胎干細胞是否可對患有中間型地中海貧血的小鼠進行組織修復。中間型地中海貧血是一種遺傳性血液紊亂,，身體缺少足夠的正常血紅蛋白,，導致血紅細胞遭到破壞及貧血。
該種方法是源自于全國兒童醫(yī)院的斯格德博士進行的研究,，胚胎干細胞來自于患有疾病的雌鼠的未受精卵,，并且確認這些干細胞系包含的僅是健康的血紅蛋白基因。這些"基因清潔"的胚胎干細胞系被轉換為細胞,，該細胞可移植入攜帶疾病的小鼠,。移植五周后的血液樣本顯示獲取的細胞出現(xiàn)在接受者的血液內。他們的血液細胞被糾正為與正常小鼠的相類似,，紅細胞計數(shù),、紅細胞比積以及血紅蛋白恢復到正常水平。
總而言之,，斯格德博士說,，我們觀察到試驗中地中海貧血病癥的持續(xù)改善，麥克考林博士說,，我們的發(fā)現(xiàn)表明,，利用生殖細胞產生胚胎干細胞，可解決的遺傳疾病的問題,，該方法與無需基因組工程的典型基因治療方法不同,。（生物谷Bioon.com）
原文鏈接：http://www.medicalnewstoday.com/articles/213370.php
譯文鏈接：http://www.chinastemcell.org/page/zixun_xwdtlist.aspx?infoid=972
生物谷推薦英文摘要：
J Clin Invest. doi:10.1172/JCI45377.
Gene therapy by allele selection in a mouse model of beta-thalassemia
Sigrid Eckardt1, N. Adrian Leu2, Ashley Yanchik2, Seigo Hatada3, Michael Kyba4 and K. John McLaughlin1,5
1Center for Molecular and Human Genetics, The Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, USA.
2University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA.
3Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
4Lillehei Heart Institute and Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
5Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
To be of therapeutic use, autologous stem cells derived from patients with inherited genetic disorders require genetic modification via gene repair or insertion. Here, we present proof of principle that, for diseases associated with dominant alleles (gain-of-function or haploinsufficient loss-of-function), disease allele–free ES cells can be derived from afflicted individuals without genome manipulation. This approach capitalizes on the derivation of uniparental cells, such as parthenogenetic (PG) ES cell lines from disease allele–free gametes. Diploid mammalian uniparental embryos with only maternally (oocyte-) or paternally (sperm-)derived genomes fail early in development due to the nonequivalence of parental genomes caused by genomic imprinting. However, these uniparental embryos develop to the blastocyst stage, allowing the derivation of ES cell lines. Using a mouse model for dominant beta-thalassemia, we developed disease allele–free PG ES cell lines from the oocytes of affected animals. Phenotype correction was obtained in donor-genotype recipients after transplantation of in vitro hematopoietic ES cell derivatives. This genetic correction strategy without gene targeting is potentially applicable to any dominant disease. It could also be the sole approach for larger or more complex mutations that cannot be corrected by homologous recombination.
