Writing 丨 Wang Cong
Edit 丨 Wang Duoyu
Types 丨 Water Text
On October 9, 2024, Professor David Baker and AlphaFold developer DEMIS Hassabis, John Jumpe won the Nobel Prize in Chemistry in 2024.
After winning the Nobel Prize three weeks, David Baker New company incubated by the laboratory - Archon Biosciences , get out of the stealth mode, Announced the completion of $ 20 million seed wheel financing.In addition, the company has also received initial funding of more than 7 million US dollars from the Protei Design Research Institute of Washington, the Washington Research Foundation, the National Health Research Institute, the Ministry of National Defense and Washington Entrepreneurship Research and Entrepreneurship Research and Entrepreneurship Research and Entrepreneurship Research and Entrepreneurship Research and Entrepreneurship Research and Entrepreneurship Research and Entrepreneurship Research and Entrepreneurship Research and Entrepreneurship Research and Entrepreneurship Research and Entrepreneurship Research and Entrepreneurship Research and Entrepreneurship Center.
The company is committed to designing a new biological drug type by the protein design platform driven by generating artificial intelligence —— antibody cage (ABC), positioning antibodies into new geometric configurations that do not exist in natural world accurately designed by artificial intelligence (AI), this design retains the combination of antibodiesFinity, at the same time, can change their distribution and retention methods in the body by adjusting the geometric shape of the anti -body cage, as well as the way of interaction with the target protein.
This technology comes from a paper published by David Baker Laboratory 3 years ago. In April 2021, David Baker The team published a research paper on the top international academic journal Science entitled: Designed Proteins Assembodies Into Modular Nanocages.
antibody cage (ABC) design is to blend the antibody constant region to the rigidity of the module toOn the ring widow, they connect them through the spiral intervals, so that the symmetrical axis of the diocyst antibody and the ring widow are in different orientations, resulting in different two -sided angles or polyhedron structures.The study successfully designed a two -sided angle, four -sided body, eight -facial body, and twenty -twenty -mandarin, which can contain 2, 6, 12, and 30 antibody molecules, respectively.The analysis of electron microscopy shows that their self -assembled nano cages are highly consistent with design and prediction.
Gray is a design protein, purple is an antibody."> The research team further verified the effect of the antibody cage. Compared with the fusion of free antibodies or FC, the antibody cage of targeted cell surface receptor enhances the apoptosis of DR5, the blood vessel production of TIE2, and CD40 activationDirector of signal with T cell proliferation.In addition, nano cages also enhanced the neutralization of SARS-COV-2 pseudo-virus by assembling SARS-COV-2 monoclonal antibodies and FC-ACE2 fusion proteins.
Compared with free antibodies, the antibody cage enhances the cell signal transfer
In terms of, this study has designed a variety of antibody cages (ABC) to form protein. By mixing the antibody with design protein, no antibody is required to modify any covalent.Nano -cage structure with controllable price and geometric shapes.Equipping the receptor -combined antibody or virus neutralized antibody to the antibody cage can significantly enhance the biological activity of these antibodies in cells, thereby enhancing the therapeutic effect of antibody drugs.
It is important to point out that David Baker Labs recently published several studies, using the AI protein design platform to design therapeutic antibodies from the beginning, and created it and founded the establishThe corresponding company.
and Archon Biosciences The company does not design or modify the antibody itself, but uses ready -made antibodies to combine it with the design combined with the design, and then itself.The cage -shaped nano structure with precise and geometric definition - antibody cage The way of action is different from traditional antibodies.
By precise control of the geometric shape, the antibody cage can achieve adjustable target protein binding and delivery, which can deliver and distribute antibody drugs and distributeTo the specific parts of the body or stay away from some parts, thereby a better use of the treatment potential of antibody drugs.
During the production process, the antibody is added to the antibody cage without modifying the protein sequence of the antibody or changing the established production process.Therefore, the assembly of the antibody cage has large -scale parallelism, easy to automate, and retains the combination of antibodies and the specificity, and can quickly explore new geometric design and spatial structure.
It is worth mentioning that David Baker Professor and Carolyn Bertozzi (2022 Nobel Prize in Chemistry)An AI pharmaceutical company called xaira therapeutics , which completed a seed wheel financing of $ 1 billion in April this year.The company is committed to re -designing the discovery and development journey of drugs through the end -to -end application of emerging AI technology.
The company publishes a Nature paper published by the company based on the David Baker laboratory.- Endotag (Endocytosis-Triggering Binding Protein), based on this, builds an artificially designed enzyme-targeted degradation chimeric — P Lytac It can target a large number of disease -related molecular targets in living cells. This technology has huge treatment potential, including the treatment of precision treatment for cancer and the treatment of autoimmune diseases and neurodegenerative diseases.
This work represents a major progress in the field of targeted protein degradation, and develops a multi-function, genetic encodingProtein degradation technology provides new possibilities for the precise treatment of a variety of refractory diseases.The goal of the research team is to continue to expand the scope of diseases applicable to Endotag, so as to provide treatment plans for more diseases.The research team also plans to explore the clinical application of Plytac, hoping to develop new therapies for treating cancer, autoimmune diseases and nervous system diseases.In addition, Endotag also helps scientists to better understand cell biology and provide new opinions for in -depth understanding of the diseased complex mechanism.This research also emphasizes the change of modern protein design -not only discovering biological functions, but also creating new biological functions.notid = "34ss92k4"> https://www.sclence.org/doi/10.1126/science.abd9994
https://www.nature.com/articles/s41586-02444-07948-2
