What is it about?

Proteins are considered as next-generation therapeutic drugs. However, the membrane of cells serve as a powerful barrier towards the entry of proteins. We have developed a method based on the addition of a simple inorganic additive, a boron cluster, which allows a well-known protein, cytochrome C, to penetrate directly through the cellular membrane and to enter the inner so-called cytosol. The uptake of this protein can be directly followed through its cellular toxicity.

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Why is it important?

The special asset of our technique is that we use a small, fully water soluble molecule to achieve protein transport. Previously, to achieve uptake, so-called nano carriers have been explored, which have two disadvantages: First, they need to be "loaded" first and a formulation has to be made. Second, their uptake generally does not occur by direct membrane permeation, but through a detour, so called endocytosis, which does not allow the proteins to reach their target. The use of boron clusters solves both problems, because the proteins and the carrier can be simply added to affect direct membrane permeation.

Perspectives

It was a great pleasure to contribute to this article and I am following with great excitement whether the method will soon be picked up by other researchers. Many methods in the field are very complex and require expensive reagents or complex procedures, but boron clusters are commercially available and should enable other researchers to test them in their laboratories by simple addition, particularly, for experiments in cell biology.

Werner Nau
Constructor University

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This page is a summary of: A small-molecule carrier for the intracellular delivery of a membrane-impermeable protein with retained bioactivity, Proceedings of the National Academy of Sciences, October 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2407515121.
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