Researchers report on cell-permeable nanobodies

July 19, 2017, Technische Universitat Darmstadt
Ring peptides open the cell membrane door allowing antibodies and other therapeutic agents to enter cells. Credit: Christoph Hohmann, Nanosystems Initiative Munich (NIM)

Scientists at the Technische Universität Darmstadt, Ludwig Maximilians University (LMU) Munich and the Leibniz Institute for Molecular Pharmacology (FMP) have managed to introduce tiny antibodies into living cells. The researchers now report on the synthesis and applications for these nanobodies in Nature Chemistry.

Antibodies are one of the main weapons of the immune system. They dock to viruses, bacteria and other invaders that course through the blood, and thereby render them harmless. Antibodies also play a key role in the diagnosis and treatment of diseases and in research. "One clear limitation is that due to their size and various other factors, antibodies are unable to permeate living ," says M. Cristina Cardoso at the TU Darmstadt. Working in close collaboration with the research group led by Christian P. R. Hackenberger at the FMP Berlin, Professor of Chemical Biology at the Humboldt University of Berlin, the inter-disciplinary team has now, for the first time, managed to permeate living cells with small antibodies, also called nanobodies, and observe them microscopically. Medicine has extremely high hopes for these tiny . Although they do not occur in the human body, they have been found in camels and in cartilaginous fish.

"In order to open up the path into the cell for the nanobodies, we decorated them chemically with cyclic cell-permeating peptides that effectively act as keys to the direct permeation through the cell membrane into the cells," explains Christian Hackenberger. As the researchers report in the current issue of Nature Chemistry, the key peptides are either coupled stably to the nanobodies or, more loosely, so that the connection is dissolved on the inside of the cell.

The scientists successfully permeated living mouse and human cells with nanoantibodies, and examined their benefits. Cell-permeable nanobodies are suited both to the recognition and manipulation of antigens and to the analysis of -protein interactions. The researchers were able to observe the interaction between the tumour inhibitor p53 and its counterpart, protein HDM2, using the nanobodies and special fluorescent markings. This interaction plays an important part in the development of cancer.

Nanobodies are also highly promising medically because they are able to transport proteins to living cells. The symptoms of Rett syndrome, for instance, a genetic disease with aspects of autism, could possibly be reduced by the protein Mecp2. The researchers permeated mouse cells with Mecp2 bound to nanobodies, and were able to prove that the protein was still intact and it reached its target in the cell. According to the report in Nature Chemistry, the cell-permeable nanobodies are general tools that deliver therapeutically relevant proteins into . This opens up a new door to treatments for diseases that have so far been untreatable.

Explore further: Scientists isolate new antibodies to fight human respiratory syncytial virus (RSV)

More information: Henry D. Herce et al. Cell-permeable nanobodies for targeted immunolabelling and antigen manipulation in living cells, Nature Chemistry (2017). DOI: 10.1038/nchem.2811

Related Stories

Relocation of proteins with a new nanobody tool

April 11, 2017

Researchers at the Biozentrum of the University of Basel have developed a new method by which proteins can be transported to a new location in a cell. The novel tool enables scientists to study the function of proteins depending ...

Nanobodies from camels enable the study of organ growth

November 9, 2015

Researchers at the Biozentrum of the University of Basel have developed a new technique using nanobodies. Employing the so-called "Morphotrap", the distribution of the morphogen Dpp, which plays an important role in wing ...

Cancer gene therapy from camels

July 14, 2011

Nanobodies produced from camel blood have unique properties, which can be used in future drug development. New research published in Journal of Controlled Release confirms that camel blood can help scientists in the fight ...

Recommended for you

Hydrogel may help heal diabetic ulcers

March 20, 2018

A hydrogel invented at Rice University that is adept at helping the body heal may also be particularly good at treating wounds related to diabetes.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.