# CRISPR-Cas editing technologies for viral-mediated gene therapies of human diseases: Mechanisms, progress, and challenges

## TL;DR

This paper reviews recent advances in gene therapy using CRISPR-Cas technologies and viral vectors like AAVs and LVs, highlighting their potential and challenges in treating genetic diseases.

## Contribution

The paper provides a comprehensive review of viral-mediated CRISPR-Cas gene therapies, emphasizing their mechanisms, progress, and current clinical challenges.

## Key findings

- CRISPR-Cas technologies are advancing gene therapy for genetic diseases.
- AAVs and LVs are the primary viral vectors used in approved gene therapies.
- Challenges remain in clinical application, including manufacturing and delivery efficiency.

## Abstract

The gene therapy landscape has evolved substantially in recent years, beginning with the approval of the first adeno-associated virus-based gene therapy, Luxterna, in 2017. Since then, the US FDA has approved nearly 30 new viral gene therapy programs, with notable examples including Zolgensma, Spinraza, Hemgenix, Zynteglo, Lyfgenia, Kymriah, Skysona, and Tecelra. Remarkably, all these products rely on delivery via adeno-associated vectors (AAVs) and lentiviral vectors (LVs). Improvements in viral-mediated gene transfer efficiency and clinical-scale manufacturing, together with immense commercial interest, have greatly propelled the clinical adoption of gene therapy products. In recent years, clustered regularly interspaced short palindromic repeats (CRISPR) and its related Cas proteins (CRISPR-Cas) have made significant advances in gene therapy, offering next-generation approaches for curative gene editing to treat genetic diseases and disorders. In this review, we examine the range of these therapeutics and their viral carriers, focusing primarily on LVs and AAVs. We provide a snapshot of the current status of the field and highlight some of the current challenges in the clinical application of gene therapy, with particular emphasis on viral CRISPR-Cas-based technologies and their future potential.

In this review, Kantor and colleagues highlight some of the current challenges faced in the preclinical and clinical uses of gene therapy, with particular emphasis on viral-CRISPR-Cas-based technologies and their future potential. They delve into the assortment of technologies and viral carriers, mostly focusing on lentiviral and adeno-associated vectors.