Targeting EGFR/HER2/HER3 with a three-in-one aptamer-siRNA chimera

Description:

Current State of the Art

Treatments that target one protein or gene are effective for some cancer and infectious disease. However, clinical studies showed that many patients do not respond or develop resistance to one-target treatments. Therapies with more than one targets are needed to improve clinical efficacy and expand clinical application.

 

Problems with the Current Art

To this end, biopharmaceutical companies are pursuing bispecific and pan antibody therapies: one pan-HER antibody mixture is in the clinical trial; one bispecific antibody for the treatment of B-cell acute lymphoblastic leukemia is approved by the FDA in 2015. Current antibody therapies are expensive. There is a clinical need for more affordable and effective targeted treatments. 

 

Advantages of Our Invention

The scientists at Augusta University invented a composition matter and a novel therapy platform that specifically targets three molecules simultaneously and is less expensive than antibodies. In this construct, a single EGFR siRNA is placed between HER2 and HER3 aptamers to create a HER2 aptamer-EGFR siRNA-HER3 aptamer chimera.  HER2 and HER3 aptamers deliver EGFR siRNA specifically to HER2 and HER3 over-expressing cells to release EGFR siRNA. As a result, the chimera simultaneously inhibits HER2, EGFR, and HER3.

 

In both in vitro cell culture and in vivo xenograft studies, the chimera inhibited the expression of EGFR and the activation of HER2 and HER3 signaling, thereby effectively reduced breast cancer growth. Compared to antibodies, the aptamer and siRNA nucleotides have low immunogenicity and are easier and less expensive to produce.

 

Moreover, the scientists can change the aptamer and siRNA sequence and tailor the construct to target an array of proteins including oncogenes, proto-oncogenes tumor-specific antigens and viral antigens, making the aptamer-siRNA chimera a promising therapy platform.

AURI: 2018-008

 

Patent Information:
Category(s):
Therapeutics
For Information, Contact:
Lei Wan
Technology Transfer Associate
Augusta University
lewan@augusta.edu
Inventors:
HongYan Liu
Keywords:
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