A Spider’s ‘Bite’ Sends Antibodies Into Cells

Scientists have used reengineered spider venom toxin to help antibodies escape endosomes once inside the cell.

AsianScientist (May 31, 2017) – Scientists at Kyoto University have used a reengineered spider venom peptide to deliver biomacromolecules such as antibodies into a cell. Their strategy, published in Nature Chemistry, not only allows researchers to track the antibodies visually, but also makes it possible for the antibodies to interact with target proteins, modulating their functions.

Our cells are rich in proteins which are potential targets for therapy. However, studying the behavior of these proteins using externally delivered biomacromolecule has often been stymied by the difficulty of gaining access to the interiors of living cells.

“Efficient labeling of intracellular proteins with antibodies allows us to dramatically improve our understanding of their behavior and significance,” explained study first author PhD student Ms. Misao Akishiba. “Cells can take in antibodies through membrane-bound vesicles called endosomes. But normally once inside these endosomes, the antibodies have trouble escaping.”

The researchers found that a simple redesign of a spider venom peptide named M-lycotoxin enables the efficient release of antibodies from their endosome cages.

“We took M-lycotoxin and replaced a leucine residue with glutamic acid, which we then called L17E. When L17E enters the cell, it specifically interacts with endosome membranes, breaking them down and releasing the antibodies,” Akishiba said.

The research team then showed that functional antibodies, such as those involved in suppressing gene expression, could be delivered as well.

“This will benefit not only basic science, but also the development of new treatments and drugs,” concludes team leader Professor Shiroh Futaki. “Moreover, this tool could potentially be used to transport other bioactive macromolecules—and even nanoparticles—into cells.”

As a next step, the researchers hope to improve the efficiency of macromolecule uptake by endosomes, thereby increasing the amount of cargo that can be transported.

The article can be found at: Akishiba et al. (2017) Cytosolic Antibody Delivery by Lipid-sensitive Endosomolytic Peptide.


Source: Kyoto University.
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