A Scoping Review on the Ethical Issues in the Use of CRISPR-Cas9 in the Creation of Human Disease Models

Abstract

Introduction: The remarkable advances in molecular science and technology have dramatically changed the landscape of Deoxyribonucleic Acid (DNA). With the rapid pace of new gene editing technologies like Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9 (CRISPR-Cas9), human disease models can be created to reduce the burden of morbidity and mortality caused by genetic defects and congenital malformations. However, despite its potential to advance human health and well-being, the use of CRISPR-Cas9 technology raises numerous ethical concerns, including the lack of a well-defined regulatory framework. Aim: To outline the ethical concerns that arise in the creation of human disease models using CRISPR-Cas9 technology and to design a conceptual framework to identify the ethical challenges and address these concerns. Materials and Methods: The data on ethical issues in the use of CRISPR-Cas9 in the creation of human disease models were obtained by reviewing 530 articles retrieved from scientific databases such as Google Scholar, PubMed, Scopus, and Excerpte Medica dataBASE (EMBASE) from the year 2015. Based on the eligibility criteria, 24 publications from 56 full-text articles that were screened were included in this study. The selection process was conducted in three phases-screening of the title, abstract, and full text. The articles selected after full-text screening were analysed, and the data was scrutinised independently. Tables, charts, figures, and graphs were used to organise and illustrate the obtained data. The entire paper was drafted using the Preferred Repoting Items for Systematic Reviews and Meta-analyses (PRISMA) extension for scoping review reporting criteria. Results: The present study included 24 articles for review after the screening process. The articles emphasised the bioethical issues related to CRISPR-Cas9 technology and gene editing while also shedding light on the current level of research in the field. The studies included different countries, with the maximum number of papers from the United States of America (USA), followed by the United Kingdom (UK), China, Turkey, Spain, Canada, Pakistan, Australia, Italy, France, Korea, and Sri Lanka. These articles were published between 2015 and 2021. The disease for which models were created was not mentioned in the majority of articles, while a few investigated the application of CRISPR-Cas9 in genetic disorders, cardiovascular diseases, neurodegenerative diseases, and eye disorders. The major ethical concerns identified included safety, efficacy, unintended consequences, harm to the environment, off-target effects, obtaining informed consent, and the risk of misuse. Conclusion: The use of CRISPR-Cas9 technology in creating human disease models has raised many ethical concerns. One of the primary ethical issues is the potential for unintended consequences, which could have serious long-term effects on individuals and their offspring. To address these ethical issues, it is important to develop ethical guidelines and best practices, as well as to support ongoing research to investigate the longterm effects of gene modifications.