Developing CRISPR-Based Therapies for Genetic Diseases: Clinical Trials and Regulatory Challenges

Abstract

CRISPR-based therapies have emerged as transformative tools for treating genetic diseases, yet their clinical implementation presents a complex interplay of scientific promise and regulatory scrutiny. This study analyzed 58 registered clinical trials employing CRISPR-Cas systems for therapeutic purposes, focusing on trial characteristics, delivery methods, gene targets, geographical distribution, and regulatory challenges. The majority of trials targeted oncological (37.9%) and hematological (20.7%) disorders, with over 65% in early-phase development (Phase I or I/II).Ex vivo methods based on lentiviral vectors and electroporation differed from in vivo approaches mainly on a basis of adeno-associated viruses (AAV) or lipid nanoparticles.  Gene modifications with emphasis on PD-1, important for cancer immunotherapy, and BCL11A prioritized in hemoglobinopathy repair.  Based on stakeholder interviews off-target risk was the greatest regulatory barrier (87%), followed by long-term monitoring (76%) and delivery safety (72%).  Central ethical issues consisted of concerns regarding the processes of informed consent, participants’ unequal access, and the moral aspects of germline editing.  Medians of existing studies showed a 67% editing efficiency, 18% adverse events, and a meager completion rate of 62% for trials.  Despite these impediments, more than half, approximately 60%, of the respondents from regulatory, clinical, industry, and ethics communities supported increased trials – provided rigorous preventative measures are upheld.  Based on this research, it’s clear that it takes harmonized regulations, continued safety surveillance, and designs rooted in ethical value to safely and equitably introduce CRISpen-based technologies.  This paper provides working suggestions on how CRISpen could be used, safely and efficiently in clinical environments and reveals how CRISpen is moving from experimental research to effective therapies.