UCLA researchers in the Department of Bioengineering have developed a novel microneedle patch that effectively delivers nucleic acids across the skin for use as a delivery platform for gene therapies.
BACKGROUND
Gene therapies work by delivering designed corrective nucleic acid sequences to cells expressing mutant disease-causing forms of genes. For gene therapy to fulfill its curative function, the therapeutic must be explicitly delivered to those cells targeted by the treatment. Strategies including the use of viral vectors have been exploited to target nucleic acids to required cell types. However, immunogenicity and biosafety are concerns associated with the use of targeting mechanisms of viral origin. Strategies using nonviral gene therapy vectors are promising for developing gene therapies in diverse tissue types.
One organ system, the skin, is a complex tissue arrangement containing extensive vasculature and networks of the lymphatic system that houses diverse cell types often targeted by gene therapies: including high numbers of immune cells. The tissue is also the site of numerous malignancies and disorders, including infections, cancers, wounds, and other genetic skin conditions with potential for treatment through gene therapy-based methods. Due to its proximity to the body's surface, the organ system is also a strong candidate for drug delivery systems using local application targeting. However, transdermal delivery remains challenging because of the tough protective skin layers. Delivery systems that can achieve transdermal delivery could enable next-generation gene therapies targeting pathologies in the previously untreatable skin because of low delivery efficiency across the dermal layers. Therefore, developing new safe and efficient strategies for transdermal nucleic acid delivery fulfills a significant need in gene therapy research.
INNOVATION
UCLA researchers in the Department of Bioengineering have developed a micro-needle-based patch that enables the delivery of nucleic acids across the dermal layer for use as a gene therapy carrier. The biodegradable patch is designed to be administered at the site of diverse skin pathologies to physically deliver therapeutic nucleic acids to the site of need. The platform makes use of gelatin methacryloyl (GelMA) composed of microneedles containing embedded DNA-encapsulated poly(B-amino ester) (PBAE) nanoparticles for controlled, local, transdermal delivery of plasmid DNA. Notably, the invention invokes high local transfection efficiencies both in vivo and in vitro. As a direct consequence, the proposed micro-needle-based patch could serve as a practical next-generation gene therapy approach.
POTENTIAL APPLICATIONS:
• A transdermal delivery platform for gene therapies.
ADVANTAGES:
• Relatively non-invasive delivery method.
• Does not rely on potentially dangerous viral vectors.
• High transfection efficiency at the site of application.
DEVELOPMENT-TO-DATE: UCLA researchers have demonstrated the effectiveness of delivering plasmid DNA through a microneedle delivery platform in mice. High transfection efficiencies were observed in experiments in vitro and in vivo.
RELATED PAPERS:
Qu, M. et al. Biodegradable microneedle patch for transdermal gene delivery. Nanoscale 12, 16724–16729 (2020).