Understanding Why Gene Therapy May Be Less Effective in Women: Insights from Mouse Research

Gene therapy offers promising avenues for treating various conditions, including sight loss, by utilizing harmless viruses to deliver therapeutic genes directly into diseased cells, restoring normal function. However, clinical trials have shown that gene therapy can sometimes cause serious side effects in certain patients. A key factor is the patient's immune response, which may recognize the viral vectors as foreign and attack them, leading to adverse reactions.

To address this challenge, researchers have investigated the underlying immune mechanisms, particularly focusing on sex and age differences. Recent studies in mice have revealed that older female mice are more susceptible to damaging side effects following eye gene therapy compared to their male and younger female counterparts. These reactions were linked to specific differences in immune system functioning.

In experiments, both male and female mice at various ages received gene therapy injections into the eye. Results showed that young female mice exhibited heightened immune activation even at lower doses, mirroring findings in human blood samples where women’s immune cells tend to produce more inflammation. As mice aged, the inflammatory response intensified and persisted longer, especially in older females. Detailed analysis of immune cells indicated that in older female mice, these cells displayed earlier stress responses and stronger inflammation, correlating with tissue degeneration.

These findings suggest that women—particularly older women—may face increased risks of adverse effects from gene therapy, especially at doses necessary for treatment efficacy. Such outcomes are consistent with other research demonstrating women’s immune systems often respond more robustly to treatments, recognizing therapeutic agents as foreign and attacking them.

Underlying these observations are biological differences in immune function driven by sex hormones like estrogen and testosterone, as well as genetic factors such as the presence of two X chromosomes in females. Age further complicates immune responses by diminishing the ability of immune cells to recognize and eliminate foreign pathogens, leading to chronic inflammation associated with age-related diseases.

Recognizing these differences is crucial because women have historically been underrepresented in biomedical research, creating gaps in understanding treatment outcomes. Findings like these help explain why certain medications are less effective in women and highlight the importance of personalized approaches considering sex, age, and immune status.

These insights from animal studies point toward the need for tailored strategies to improve gene therapy safety and effectiveness across diverse patient groups. Ongoing research aims to develop methods to modulate immune responses, minimizing side effects while maximizing therapeutic benefits.

Source: https://medicalxpress.com/news/2025-08-gene-therapy-effective-women-mice.html