challenges of creating cellular disease models using CRISPR

challenges of creating cellular disease models using CRISPR
mahyar ansari,^1,*
1. departmant of biology, faculty of science , shahid bahonar university
Introduction: The use of CRISPR system has advantages in the field of disease modeling . The researchers used CRISPR to build models of human disease by knock-in , knock-out and indel mutations . So CRISPR/Cas9 can be used to create cancer-causing mutation in human cell lines and animal models . The CRISPR/Cas9 system has been recently used in disease-focused research to product and characterize patient-drived IPSCs with a specific genetic disease . The discover of human IPS cells in recent decades has opend a new window into disease modeling . The IPS cells have been generated as an in vitro disease model for disease such as Duchene disease and Down syndrome/trisomy 21 . These cell can be adapted to drug discovery with help of high throughout compound screening technology . The IPSCs cells have good advantage for pesonalized medicine because they can be derived from the patient themselves and thus do not stimulate the immune system when transplanted. But these model have some challenges.The purpose of this review article is to examine the challenges of creating cellular disease models using CRISPR.
Methods: In this review, pubmed, sciecedirect and wiley library sites were used. The keywords used to search these sites were crispr and disease model. After collecting the articles, the challenges in this field were studied.
Results: In disease modeling , it is possible that IPSCs derived from a disease caused by mutation. The main drawback here is that there is a difference in the genetic backgrounds of the control and disease groups ,a major problem in the study of human disease in the cell culture field is in long-term latent disease such as Alzheimer's , that it is be difficult to in vitro . Also IPS cell are limited in reusing complex tissue arthitecture in terms of cell complexity. This limitation has challenged the analysis of physiological and system-level phenotype .The one of IPS cells that use to cell disease creation are human ips cells (hIPSC) . These cells have some disadvantage . Limited sample size is one of the major disadvantages of these cells. In addition, to ensure the production of hIPSC cell lines, extensive validation is required, such as differentiation potential, lack of re-planning, and so on. The production and approval of hIPSC is time consuming and expensive. Another problem with hipsc studies is that an unexpected amount of variability may occur .
Conclusion: Genome manipulation in IPS cells or cultured in vivo has the potential to treat disease. Especially disease caused by single gene mutation. Patient drived IPS cells can be modified with CRISPR technology , selected in vitro and returned to the patient for replacement instead of disease cell .Although the latest genome editing tool has been used in the production of cellular and animal models, but the therapeutic ability of genome editing has still been delayed due to biological and ethical barriers. Another important issue is the ethical concern about the use of CRISPR technology in humans. Advances in genome repair will allow us to learn more about the development and pathogenesis of the disease .
Keywords: CRISPR , IPS , disease , model