Transcriptionally Targeted and CPG-free Plasmid for Theranostic Gene Therapy

Unmet Need
Hepatocellular carcinoma (HCC) is the third leading cancer in the US with a ~twenty percent (20%) survival rate. HCC develops typically in the inflammatory environment of the liver caused by infections or liver disease. Therefore, it is essential to have highly targeted anti-cancer therapies to achieve clinical efficacy. Currently, viral gene therapy used in HCC has poor response, high toxicity, and poor outcomes due to inadequate gene delivery vectors, inadequate delivery methods, immunogenicity, and targeted cell specificity.  To overcome the challenges of traditional clinical therapies, improved biodegradable nanoparticles and non-viral nucleic acid therapeutics provide promising treatment through effective delivery of theranostic genes in liver cancer.
 
Technology Overview
JHU researchers developed an improved and effective method for delivery of nucleic acid therapy to hepatocellular carcinoma (HCC) cells without toxicity and furthering liver failure. JHU researchers used biodegradable nanoparticles as a delivery system selective towards HCC cells over healthy cells. In addition, polymeric nanoparticles, an improved non-viral gene (DNA plasmid) therapy enclosed within the nanoparticles are used to treat HCC.
 
Stage of Development
The inventors have preliminary data showing the efficacy of an improved nanoparticle delivery system and nucleic acid therapy for HCC. Inventors have tested a library of distinct biodegradable polymers to show efficient delivery using in vitro (cell lines) and in vivo (mouse models) studies. In regards to gene therapy efficacy, JHU researchers developed a specific non-viral nucleic acid sequence (DNA plasmid) that minimize immunogenicity, cytotoxicity, and increased cell death in vitro on multiple human HCC cell lines. More studies should be conducted on other tumor cell types to prove the efficacy of nanoparticle as a delivery method for gene therapy.
Publications
El-Serag, et. al., Gastroenterology. 2007 Jun; 132(7):2557-76.
 
Zamboni GC, et. al., J Control Release. 2017 Oct 10; 263:18-28.
 

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