2020-118 AN INTRAVENOUS SYSTEMIC DELIVERY VEHICLE FOR INTRACELLULAR GENE THERAPY

SUMMARY

Researchers in the UCLA Department of Microbiology Immunology and Molecular Genetics have devised a nanocapsule gene therapy vehicle that allows targeted intravenous delivery without ex vivo manipulation.

BACKGROUND

Currently, nearly all therapeutic applications for gene delivery in clinic are conducted ex vivo, which is by removal of cells from the body, transducing genes and then transplanting them back into the body. This is the typical clinical practice for many therapeutic methods, such as hematopoietic stem progenitor cells transplant for genetic diseases and T cell transplant for delivery of chimeric antigen receptors. However, such ex vivo practice results in a much longer treatment time and higher risk of cell damage since the cells are exposed to the outside. Therefore, a new in vivo gene therapy vector is needed for a faster treatment and less risky gene delivery method.

INNOVATION

UCLA researchers have engineer a bilayer nanocapsule which has unique properties to allow intravenous delivery, maintain in vivo, and target cells without ex vivo manipulation. The inner layer is positively charged and allows the transduction of DNA, RNA, or protein cargo. The outer layer is a neutral membrane and is conjugated to the inner core, forming an energetically stable bilayer structure. The outer layer can be removed under hydrolytic condition, and the inner positively charged core are exposed and allows transduction of the cargo components. 

POTENTIAL APPLICATIONS

• Delivery vehicle for gene therapies
• Delivery vehicle for different therapeutic options i.e. biologics, monoclonal antibodies and/or small molecules that target CNS metastases (primary and secondary) and lymph nodes

ADVANTAGES

• Enhanced stability due to bilayer structure
• Targeted gene therapy
• Sustained drug delivery at the site of tumor
• Inert
• Resistant to protein adsorption
• Does not illicit an immune response

DEVELOPMENT-TO-DATE

The delivery system prototype has been assembled and successfully demonstrated, and the relating work has been submitted for publication.

Related Papers (from the inventors only)

1. Wu D, Qin M, Xu D, Wang L, Liu C, Ren J, Zhou G, Chen C, Yang F, Li Y, Zhao Y, Huang R, Pourtaheri S, Kang C, Kamata M, Chen ISY, He Z, Wen J, Chen W, Lu Y. A Bioinspired Platform for Effective Delivery of Protein Therapeutics to the Central Nervous System. Adv Mater. 2019;31(18):e1807557.
2. Wen J, Wu D, Qin M, Liu C, Wang L, Xu D, Vinters H, Liu Y, Kranz E, Lee Y, Guan X, Sun G, Sun X, MartinezMaza O, Widney D, Lu Y, Chen I, Kamata M. Delivering therapeutic mAb to control cancer with CNS metastases, Nature Biomedical Engineering. 2019; In Press.