Rice University scientists have found a simple method to attach drugs or other substances to antibodies, the powerful proteins that are central to the body's immune system .
The Rice lab of bioengineer Han Xiao developed a technique called pClick, which uses a cross-linker that snaps to a specific site on antibodies and serves as a bridge to therapeutic molecules or nanomaterials without the need to re-engineer the antibody with harmful chemicals, enzymes or ultraviolet (UV) light.
All of those alternatives are used by companies and researchers to prepare antibodies for the conjugation -the process of chemically modifying them. "But our technology is straightforward , highly efficient and economical," said Xiao, who joined Rice last year with funding from the Cancer Prevention and Research Institute of Texas (CPRIT).
Body's immune system
"We use native antibodies with no engineering, no enzyme treatment, no chemical treatment , no UV treatment." We have not needed them, "said Xiao.
The research is detailed in the American Chemical Society journal Bioconjugate Chemistry . Antibodies are dimers, similar proteins that in this case come together in a "And" shape, and the workhorses of the immune system.
Their job is to recognize and bind to pathogens , facilitating the invaders' elimination. Antibodies either roam the bloodstream or attach themselves to cells that need protection. Because they are ubiquitous in the body, modifying them is a way to treat disease.
That's not easy, Xiao said. "For the first generation of antibody conjugation , people used targets like lysine or cysteine residues to attach their therapeutic molecules," Xiao said. "But antibodies are so big, and there are so many lysine and cysteine residues, they can not control their positions.
Rice University bioengineer Han Xiao and his team developed the simple pClick technique to attach drugs or other substances to antibodies, the powerful proteins that are central to the body's immune system .
He said second-generation research focused on site-specific conjugation to therapeutic drugs at a particular location on the antibody. "That let them optimize the position of the drug, but to do so people needed to know the antibody's sequence and engineer it," Xiao said.
"Our next-generation work addresses two problems," he said. "First, we do not have to engineer antibodies . We use antibodies from the market for direct, site-specific conjugation. Second, we know exactly our Where goes on the antibody molecule."