科學(xué)家正在研究從疾病個(gè)體中提取的誘導(dǎo)多能干細(xì)胞（iPSCs）,，為了探究疾病如何發(fā)展和它們可能進(jìn)行的阻止或逆轉(zhuǎn)疾病進(jìn)程的干預(yù)。然而,，用這種方式研究某些疾病仍然面臨挑戰(zhàn),。比如，在一些人類(lèi)疾病中,，一個(gè)突變基因并不總是導(dǎo)致的疾病,，而有其他一些疾病，則傾向于在晚年發(fā)病,。這種情況下,，科學(xué)家們希望將包含突變基因的細(xì)胞與包含正常的基因細(xì)胞對(duì)比。但微妙的疾病特征可能只有當(dāng)細(xì)胞的遺傳背景被小心控制時(shí)才會(huì)顯現(xiàn),。
現(xiàn)在,，科學(xué)家已經(jīng)可以利用基因工程制造用以對(duì)比的兩種類(lèi)型的理想控制細(xì)胞，除致病基因以外它們的基因完全相同,。研究人員利用遺傳性帕金森氏?。≒D）病人的皮膚細(xì)胞產(chǎn)生PD- iPSCs。然后,，他們糾正PD- iPSCs的突變,。繼而誘導(dǎo)PD- iPSCs和已糾正iPSCs生成神經(jīng)細(xì)胞。這樣,，他們就可以研究來(lái)自同一個(gè)體的攜帶疾病基因的與疾病基因已糾正的神經(jīng)細(xì)胞的特點(diǎn),。科學(xué)家們還利用基因工程來(lái)生成,，除攜帶兩種不同PD遺傳基因外,，基因完全相同兩個(gè)的人類(lèi)胚胎干細(xì)胞（hESC）株，與原來(lái)的野生型（正常）人類(lèi)胚胎干細(xì)胞細(xì)胞進(jìn)行比較,。
使用新的細(xì)胞株作為工具,，科學(xué)家們可以仔細(xì)比較，以了解這些突變?nèi)绾螌?dǎo)致疾病,。這項(xiàng)研究還表明,，糾正在人類(lèi)細(xì)胞中的致病突變是可行的。（生物谷Bioon.com）
doi:10.1016/j.cell.2011.07.035
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Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations.
Patient-specific induced pluripotent stem cells (iPSCs) derived from somatic cells provide a unique tool for the study of human disease, as well as a promising source for cell replacement therapies. One crucial limitation has been the inability to perform experiments under genetically defined conditions. This is particularly relevant for late age onset disorders in which in vitro phenotypes are predicted to be subtle and susceptible to significant effects of genetic background variations. By combining zinc finger nuclease (ZFN)-mediated genome editing and iPSC technology, we provide a generally applicable solution to this problem, generating sets of isogenic disease and control human pluripotent stem cells that differ exclusively at either of two susceptibility variants for Parkinson's disease by modifying the underlying point mutations in the α-synuclein gene. The robust capability to genetically correct disease-causing point mutations in patient-derived hiPSCs represents significant progress for basic biomedical research and an advance toward hiPSC-based cell replacement therapies.
