科学家正在研究从疾病个体中提取的诱导多能干细胞（iPSCs），为了探究疾病如何发展和它们可能进行的阻止或逆转疾病进程的干预。然而，用这种方式研究某些疾病仍然面临挑战。比如，在一些人类疾病中，一个突变基因并不总是导致的疾病，而有其他一些疾病，则倾向于在晚年发病。这种情况下，科学家们希望将包含突变基因的细胞与包含正常的基因细胞对比。但微妙的疾病特征可能只有当细胞的遗传背景被小心控制时才会显现。
现在，科学家已经可以利用基因工程制造用以对比的两种类型的理想控制细胞，除致病基因以外它们的基因完全相同。研究人员利用遗传性帕金森氏病（PD）病人的皮肤细胞产生PD- iPSCs。然后，他们纠正PD- iPSCs的突变。继而诱导PD- iPSCs和已纠正iPSCs生成神经细胞。这样，他们就可以研究来自同一个体的携带疾病基因的与疾病基因已纠正的神经细胞的特点。科学家们还利用基因工程来生成，除携带两种不同PD遗传基因外，基因完全相同两个的人类胚胎干细胞（hESC）株，与原来的野生型（正常）人类胚胎干细胞细胞进行比较。
使用新的细胞株作为工具，科学家们可以仔细比较，以了解这些突变如何导致疾病。这项研究还表明，纠正在人类细胞中的致病突变是可行的。（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.
