Genetically modified helminths as pharmaceutical biofactories

Area of Science:

• Biotechnology
• Parasitology
• Drug Delivery Systems

Background:

• Traditional drug delivery faces challenges like poor absorption, first-pass metabolism, and non-specific targeting.
• Live biotherapeutic products, such as transgenic bacteria, are emerging as novel drug delivery methods.
• Human helminth infections are safe and may possess natural protective qualities for various diseases.

Purpose of the Study:

• To review the potential of wild-type and genetically engineered helminths as drug-delivery platforms.
• To explore the application of genetic engineering, specifically CRISPR, for modifying helminths.
• To focus on human hookworms and schistosomes for therapeutic protein delivery.

Main Methods:

• Review of existing literature on helminth infections and clinical trials.
• Discussion of genetic engineering techniques (CRISPR) for helminth modification.
• Analysis of helminth excretory/secretory proteins (ESP) and their immune-modulating properties.

Main Results:

• Helminths naturally release ESPs that modulate the host immune system.
• Genetic modification allows parasitic helminths to constitutively release therapeutic biologics.
• Controlled human helminth infections are safe and well-tolerated.

Conclusions:

• Genetically engineered helminths represent a promising novel drug-delivery platform.
• This approach could offer new treatments for inflammatory bowel disease, type 2 diabetes, coeliac disease, and arthritis.
• Human hookworms and schistosomes are key species for developing these therapeutic platforms.