Monobodies are synthetic binding proteins in which fibronectin type III domain (FN3) is used as a molecular scaffold. Monobodies are robust alternative to antibodies to create target-binding proteins. The term monobody was devised by Koide group in 1998. Monobody belong to a class called antibody mimics aiming to overcome the shortcomings of natural antibody. A major advantage of monobody is that it can be used as genetically encoded intracellular inhibitors. Adnexus (now a part of Bristol-Myers Squibb), uses monobody technology to inhibit tumor angiogenesis since 2007.
Monobody – a technology with great potential in Cancer Treatment
Monobody is a technology which has great potential in the treatment of cancer. Monobody is independent of their environment and can be used as genetically encoded inhibitors. When a monobody binds to a protein then it work as an inhibitor of that protein.
Pegdinetanib, also known as Adnectin, is an antagonist of vascular endothelial growth factor receptor 2 has entered in clinical trial II for the treatment of glioblastoma. Adnectins is based on 10th fibronectin type III domain designed to bind with high affinity and specificity to relevant targets. There are three solvent accessible loops (BC, DE, and FG) which are responsible for binding. Various monobody proteins have been developed for clinical efficacy against cancer and infections. The market of monobody will be high in developed region like America because of availability of advance medical technology, good medical facilities and medical infrastructure.
Success of therapeutic antibodies has sparked a growing interest to create molecules that bind to the target molecule specifically and efficiently. A common alternative process is that the libraries of monobody being constructed which can be obtained by capturing natural diversity of an antibody.
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Research in the field of Monobody
Researchers at the University of Illinois, Chicago identified a monobody, NS1, which can block oncogene activity. 30% of all cancers are due to RAS mutation. RAS mutation is also found in 90% of pancreatic cancers and frequently occurs in colon cancer, lung cancer and melanoma. The NS1 monobody bind to RAS protein molecule and inhibits its oncogenic activity.
Monobody – a better alternative
Antibodies are successful tools used in diagnostics, purification, and therapeutics. Antibodies have their limitations also like high product cost and low stability. Alternative tools based on nucleic acid (aptamers), polypeptides (engineered binding proteins) and inorganic matrices have received attention recently. With increasing research activities for drug development in cancer, more information would be gathered with respect to monobodies too. Because of high specificity and affinity monobodies have potential and can be used in organ transplant in near future and can affect the antibodies market. Successful outcomes will boost investors to develop this technology and address the unmet need of cancer patients undergoing antibody therapy. Use of monobodies as therapeutic drug improves patient situation and hence companies are striving to develop monobodies to be used as therapeutic drugs in the treatment of cancer.
Research and development in use of monobody-based therapies is expected to boost the market growth. For instance, in August 2019, researchers from The University of Chicago characterized 42 Flublok-induced monoclonal antibodiesand 38 Flucelvax-induced mAbs for avidity, cross reactivity, and any selectivity towards the head versus the stalk domain to compare the fine specificity of the antibodies induced by recombinant hemagglutinin vaccine produced in insect cells (Flublok) and Flucelvax, prepared from virions produced in mammalian cells.
Similarly, in August 2019, researchers from Icahn School of Medicine at Mount Sinai characterized monoclonal antibodies isolated from a patient with an active Zika virus infection that potently neutralized virus infection in Vero cells at the nanogram-per-milliliter range.
In June 2018, researchers from Bristol-Myers Squibb reported that 6200_A08, a novel gp41-binding Adnectin with potent anti-HIV activity is highly synergistic when linked to a CD4-binding Adnectin. Novel bispecific molecules of this type may serve as the next generation of potent antiviral agents.
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