科學家正在研究從疾病個體中提取的誘導多能干細胞（iPSCs），為了探究疾病如何發(fā)展和它們可能進行的阻止或逆轉(zhuǎn)疾病進程的干預。然而,，用這種方式研究某些疾病仍然面臨挑戰(zhàn)。比如,，在一些人類疾病中,，一個突變基因并不總是導致的疾病，而有其他一些疾病,，則傾向于在晚年發(fā)病,。這種情況下，科學家們希望將包含突變基因的細胞與包含正常的基因細胞對比,。但微妙的疾病特征可能只有當細胞的遺傳背景被小心控制時才會顯現(xiàn),。
現(xiàn)在，科學家已經(jīng)可以利用基因工程制造用以對比的兩種類型的理想控制細胞,，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病（PD）病人的皮膚細胞產(chǎn)生PD- iPSCs,。然后,，他們糾正PD- iPSCs的突變。繼而誘導PD- iPSCs和已糾正iPSCs生成神經(jīng)細胞,。這樣,，他們就可以研究來自同一個體的攜帶疾病基因的與疾病基因已糾正的神經(jīng)細胞的特點?？茖W家們還利用基因工程來生成,，除攜帶兩種不同PD遺傳基因外，基因完全相同兩個的人類胚胎干細胞（hESC）株,，與原來的野生型（正常）人類胚胎干細胞細胞進行比較,。
使用新的細胞株作為工具，科學家們可以仔細比較,，以了解這些突變?nèi)绾螌е录膊?。這項研究還表明，糾正在人類細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.
