YANG RESEARCH GROUP - Low Molecular Weight Protamine
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Low Molecular Weight Protamine (LMWP) as Non-Toxic Heparin Antagonist and Cell Penetrating Peptides for Drug Delivery

ATTEMPTS approach

In order to achieve more effective targeted delivery of macromolecular drugs (proteins, nucleic acids, polymer-drug conjugates), targeting and activation of therapeutic component (i.e., triggered release) are combined. The term ‘ATTEMPTS (Antibody Targeted, Triggered, Electrically Modified Prodrug Type Strategy)’ began with the system for delivery of thrombolytic enzyme (t-PA) with the aid of an antibody. Each component is conjugated to oppositely charged entities (+ charged peptides on the t-PA and heparin on the antibody) and allowed to form complexes via electrostatic interaction. Once reaching the target site, a triggering agent (i.e., protamine) is administered to release the therapeutic component so that it will act on the target. This concept is not just limited to the delivery of thrombolytic agent using antibody, but now expanded to other applications such as tumor targeting and therapy, with a variety of targeting moiety and arginine-rich cell-penetrating peptide (e.g., low molecular weight protamine; LMWP – a nontoxic heparin antagonist) for intracellular delivery of macromolecules.

Transdermal Approaches

Research to be conducted will be focused on developing a non-invasive delivery method for hepatitis B vaccination for the prevention of hepatitis B infection. Hepatitis B is the most common serious liver infection in the world. WHO estimates approximately 30% of the world's population (about 2 billion people) have serological evidence of infection with HBV, and about a million of the infected die from chronic liver disease annually, including cirrhosis and liver cancer. Thus HBV is believed to be second only to tobacco as a known human carcinogen. However multi-injection vaccination is of poor patient-compliance. Furthermore, unsafe injection accounts for 33% of new HBV infections in developing and transitional countries for a total of 21.7 million people infected each year. Therefore, vaccine delivery with easy, painless, non-invasive operation is an effective method to popularize vaccination. There is a broad recognition of the need to find ways of needle-free immunization.

Lab Members Currently Working on this Area:  Young-Min Kwon, Cheol Moon, Yongzhuo Huang