An easier way of sneaking antibodies into cells

For almost any conceivable protein, corresponding antibodies can be developed to block it from binding or changing shape, which ultimately prevents it from carrying out its normal function. As such, scientists have looked to antibodies as a way of shutting down proteins inside cells for decades, but there is still no consistent way to get them past the cell membrane in meaningful numbers.

rendering of an antibody about to go through the membrane of a cell
Getting a complex protein like an antibody through the membrane of a cell without damaging either is a longstanding challenge in the life sciences. (Image: Penn Engineering)

Now, Penn Engineering researchers have figured out a way for antibodies to hitch a ride with transfection agents, positively charged bubbles of fat that biologists routinely use to transport DNA and RNA into cells. These delivery vehicles only accept cargo with a highly negative charge, a quality that nucleic acids have but antibodies lack. By designing a negatively charged amino acid chain that can be attached to any antibody without disrupting its function, they have made antibodies broadly compatible with common transfection agents.

The study, published in the Proceedings of the National Academy of Sciences, was conducted by Andrew Tsourkas, professor in the Department of Bioengineering, and Hejia Henry Wang, a graduate student in his lab.

“If you want to study the role of a specific protein within a cell, you need a way of shutting down its function,” Tsourkas says. “Scientists have been talking about using antibodies as a way of doing that since at least the 1980s, but even the best methods today are inefficient and often invasive.”

Read more at Penn Engineering.