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What risks have appeared in some human gene therapy clinical trials?

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CRISPR-Cas9; gene editing — gene editing The CRISPR-Cas9 gene-editing complex from the bacterium *Streptococcus pyogenes*.

Human gene therapy clinical trials have revealed several significant risks and safety challenges. When a normal gene is introduced into a cell, it may integrate into a chromosomal site different from the defective allele, potentially causing a new mutation if it disrupts another functional gene.12

Specific risks observed in clinical trials include:

Immune Responses: Patients may suffer adverse immune responses to the viral vectors used to deliver genes, even when those viruses have been disabled to prevent replication.1
Leukemia-like Illnesses: In a notable trial treating infants with X-linked severe combined immunodeficiency (XSCID), some patients developed a leukemia-like illness following the therapy.1
Off-target Alterations: Research into newer technologies, such as CRISPR, is actively investigating the risks of unwanted, off-target DNA alterations that could introduce unintended genetic errors.3
Fatalities: The field has faced tragic outcomes, such as the 1999 death of teenager Jesse Gelsinger during a gene therapy trial.1

These outcomes underscore the ongoing difficulty of ensuring that gene delivery systems are both precise and safe for human subjects.1