Gene Therapy—Barriers to Somatic Gene Transfer Somatic gene therapy faces multiple technical and biological hurdles. Which of the following is the EXCEPTION (least relevant difficulty for gene therapy itself)?

Introduction / Context:
Somatic gene therapy aims to correct genetic defects by delivering functional genes into a patient’s cells. Success depends on safe, stable gene delivery and expression in appropriate target cells—often hematopoietic stem cells for systemic disorders. The question asks you to identify which listed issue is not a core difficulty of gene therapy itself.

Given Data / Assumptions:

• Gene addition strategies use viral/nonviral vectors.
• Long-term correction generally requires stem-cell targeting.
• Transduction efficiency, insertional safety, and expression control are central problems.
• GVHD is primarily a complication of allogeneic cellular grafts (e.g., HSCT), not of autologous gene-corrected cells.

Concept / Approach:
Differentiate challenges specific to gene transfer/expression from complications of allogeneic transplantation. Autologous gene therapy typically uses the patient’s own cells after ex vivo modification, thereby largely avoiding GVHD. In contrast, issues such as site-specific integration, promoter choice, vector tropism, and stem-cell transduction efficiency are intrinsic hurdles for gene therapy.

Step-by-Step Solution:

Verification / Alternative check:
Clinical gene therapy protocols overwhelmingly use autologous cells to avoid allo-immune reactions; GVHD belongs to allogeneic HSCT risk profiles.

Why Other Options Are Wrong:

• B/D/E are classic gene therapy challenges.
• C explains why stem-cell targeting is preferred for durable benefit.

Common Pitfalls:
Conflating HSCT complications with autologous gene-modified cell therapies.

Final Answer:
GVHD caused by mature T cells present in transplanted cells