The Yang Research Group - Research Interests

Red Blood Cells As Drug Carriers

L-Asparaginase Delivery Using Erythrocytes as Carrier

L-Asparaginase (ASNase) is a drug used in treatment of acute lymphoblastic leukemia (ALL). Although it has been in use for over 30 years, due to its bacterial source, immunogenicity has been a major problem. Short half-life of the enzyme also makes frequent injection necessary, exacerbating the problem. In order to address these issues, we propose encapsulating ASNase into red blood cells (RBCs). Previously, drug-induced endocytosis, electroporation, and various form of hypo-osmotic methods have been used for drug encapsulation into RBCs. However, these methods result in alterations to RBC morphology and cell membrane characteristics, which in turn increases chance for RBC removal from the system. By conjugating ASNase to protein transduction domain peptide (PTD), we can load the enzyme into RBCs with minimal changes to these parameters and thereby increase circulation time in vivo and at the same time reduce immunogenic
effect from the drug.

Long-Circulating Cocaine Esterase (CocE)

Newly discovered, potentially therapeutic enzymes may need to be conjugated with poly (ethylene glycol) (PEG) to increase duration of action and reduce undesirable hypersensitivity, as most of those enzymes are heterologous. Another way to achieve this may be encapsulation of such enzyme into erythrocytes via attachment of protein transduction domain (PTD) peptide on the enzyme either chemically or genetically (also see Tien-Yi’s description). In collaboration with the U of M pharmacology department, pegylation and TAT attachment of cocaine esterase (cocE), a potent cocaine hydrolyzing enzyme to reverse acute toxicity from cocaine overdose, is currently under way.

Lab Members Currently Working on this Area: Hee Sun Chung, Tien-Yi Lee, Young-Min Kwon