Next-generation gene therapy for infectious disease: Advances, challenges, and future directions

Area of Science:

• Infectious Diseases & Microbiology
• Genetics & Genomics
• Biotechnology

Background:

• Antimicrobial resistance and limitations of conventional treatments necessitate novel therapeutic strategies.
• Gene therapy represents a promising frontier for addressing persistent and drug-resistant infectious agents.
• HIV, HBV, HPV, and multidrug-resistant (MDR) pathogens pose significant global health challenges.

Purpose of the Study:

• To systematically review recent advancements in next-generation gene therapy for infectious diseases.
• To evaluate the efficacy, challenges, and future prospects of gene-based therapeutic approaches.
• To synthesize findings on CRISPR, bacteriophages, and RNAi in combating HIV, HBV, HPV, and MDR pathogens.

Main Methods:

• Systematic literature search adhering to PRISMA guidelines across major databases (2015-2025).
• Inclusion of 114 peer-reviewed studies, assessed using the Mixed Methods Appraisal Tool (MMAT).
• Thematic synthesis of data on therapeutic strategies, efficacy, challenges, and future directions.

Main Results:

• CRISPR-based genome editing shows potential for HIV remission in early trials.
• Engineered bacteriophages and phage-derived depolymerases exhibit efficacy against MDR bacteria and biofilms.
• RNA interference (RNAi) effectively silences Hepatitis B Virus (HBV) replication.
• Identified challenges include off-target effects, immunogenicity, scalability, and delivery barriers.

Conclusions:

• Gene therapy offers significant potential for treating infectious diseases, including those caused by resistant pathogens.
• Further research is crucial to overcome safety, efficacy, and delivery challenges.
• Ensuring equitable access to these advanced therapies, especially in low- and middle-income countries, remains a critical future direction.