Zhuo Chuanjun, Hou Weihong, Hu Lirong, Lin Chongguang, Chen Ce, Lin Xiaodong
Department of Psychiatry, Wenzhou Seventh People's HospitalWenzhou, China; Department of Psychiatry, Tianjin Mental Health Center, Tianjin Anding HospitalTianjin, China; Department of Psychiatry, Tianjin Anning HospitalTianjin, China.
Department of Biology, University of North Carolina at Charlotte Charlotte, NC, USA.
Front Mol Neurosci. 2017 Feb 3;10:28. doi: 10.3389/fnmol.2017.00028. eCollection 2017.
Schizophrenia is a genetically related mental illness, in which the majority of genetic alterations occur in the non-coding regions of the human genome. In the past decade, a growing number of regulatory non-coding RNAs (ncRNAs) including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been identified to be strongly associated with schizophrenia. However, the studies of these ncRNAs in the pathophysiology of schizophrenia and the reverting of their genetic defects in restoration of the normal phenotype have been hampered by insufficient technology to manipulate these ncRNA genes effectively as well as a lack of appropriate animal models. Most recently, a revolutionary gene editing technology known as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9; CRISPR/Cas9) has been developed that enable researchers to overcome these challenges. In this review article, we mainly focus on the schizophrenia-related ncRNAs and the use of CRISPR/Cas9-mediated editing on the non-coding regions of the genomic DNA in proving causal relationship between the genetic defects and the pathophysiology of schizophrenia. We subsequently discuss the potential of translating this advanced technology into a clinical therapy for schizophrenia, although the CRISPR/Cas9 technology is currently still in its infancy and immature to put into use in the treatment of diseases. Furthermore, we suggest strategies to accelerate the pace from the bench to the bedside. This review describes the application of the powerful and feasible CRISPR/Cas9 technology to manipulate schizophrenia-associated ncRNA genes. This technology could help researchers tackle this complex health problem and perhaps other genetically related mental disorders due to the overlapping genetic alterations of schizophrenia with other mental illnesses.
精神分裂症是一种与遗传相关的精神疾病，其中大多数基因改变发生在人类基因组的非编码区域。在过去十年中，越来越多的调控性非编码RNA（ncRNAs），包括微小RNA（miRNAs）和长链非编码RNA（lncRNAs），已被确定与精神分裂症密切相关。然而，由于缺乏有效操纵这些ncRNA基因的技术以及缺乏合适的动物模型，对这些ncRNAs在精神分裂症病理生理学中的研究以及在恢复正常表型时逆转其基因缺陷的研究受到了阻碍。最近，一种名为成簇规律间隔短回文重复序列（CRISPR）/CRISPR相关核酸酶9（Cas9；CRISPR/Cas9）的革命性基因编辑技术被开发出来，使研究人员能够克服这些挑战。在这篇综述文章中，我们主要关注与精神分裂症相关的ncRNAs，以及利用CRISPR/Cas9介导的对基因组DNA非编码区域的编辑来证明基因缺陷与精神分裂症病理生理学之间的因果关系。随后，我们讨论了将这种先进技术转化为精神分裂症临床治疗方法的潜力，尽管CRISPR/Cas9技术目前仍处于起步阶段，还不成熟到可用于疾病治疗。此外，我们提出了加快从实验室到临床应用步伐的策略。这篇综述描述了强大且可行的CRISPR/Cas9技术在操纵与精神分裂症相关的ncRNA基因方面的应用。由于精神分裂症与其他精神疾病存在重叠的基因改变，这项技术可以帮助研究人员解决这个复杂的健康问题，或许还能解决其他与遗传相关的精神障碍。
