Gene modification: Exploring the potential in treating kidney diseases

基因修饰:探索其在治疗肾脏疾病方面的潜力

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Abstract

Chronic kidney disease (CKD) is a leading cause of death worldwide. Currently available drugs slow but do not cure or prevent progression to end-stage kidney disease. Unfortunately, dialysis and kidney transplant not only pose severe lifestyle constraints and healthcare costs on patients but are also associated with side effects such as electrolyte abnormalities and increased susceptibility to infections. It is imperative to research new therapeutic strategies for the management of CKD. Technological advances in genetics and genomics in recent years have revealed the role that genetics plays in CKD pathophysiology, suggesting that gene therapies may be a viable therapeutic strategy for the management of CKD. Over the years, there has been an increase in new gene therapies approved for various indications; however, none are currently approved for kidney diseases. As our understanding of the genetics of kidney diseases grows, together with emerging gene modifying technologies and delivery tools improve, there is hope that a new generation of gene therapies may become available in the future. In this review, we describe the mechanisms of action and delivery strategies of recent gene editing technologies, after which we explore the potential of gene therapies for kidney diseases. We also discuss noteworthy adverse effects associated with gene therapies and explore the use of emerging artificial intelligence and machine learning in opening new avenues for precision editing towards treatment of kidney diseases. We conclude by discussing the challenges that may impact the development of gene therapies, along with a perspective on how the current landscape may influence the adoption of these strategies for kidney diseases.

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