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Engineering potential treatment for all four dengue serotypes

Date:
July 19, 2015
Source:
ResearchSEA
Summary:
A multinational research team comprising scientists, engineers and drug developers have joined forces to develop a viable dengue therapeutic that targets all dengue serotypes.
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A multinational research team comprising scientists, engineers and drug developers have joined forces to develop a viable dengue therapeutic that targets all dengue serotypes1. This is welcome news as dengue now spans the entire tropical world and an estimated 400 million people are infected each year. Despite the numbers, there remains no licensed treatment for dengue patients. However, this problem may soon be solved by promising findings published in the journal Cell.

Researchers from the Singapore-MIT Alliance for Research and Technology (SMART), DukeNUS Graduate School of Medicine (Duke-NUS), National University of Singapore (NUS) and Nanyang Technological University (NTU) have collaborated with the Massachusetts Institute of Technology (MIT) and a biotechnology company, Visterra, to develop a single treatment.

The team started with a naturally occurring antibody that reacted only against limited number of types of dengue virus. Using that antibody as a scaffold, the team engineered a new antibody that reacts against all four types of dengue virus. The engineering was made possible by computational methods developed in MIT and SMART. This was then confirmed and validated using a detailed crystal structure of the antibody-virus protein complex obtained at NTU, which also provided insights into how the antibody engaged the virus to produce the desired effect. Using a variety of systems developed in the SMART laboratories in the Campus for Research Excellence And Technological Enterprise (CREATE) (e.g. the SMART humanised mouse model), Duke-NUS and NUS, the team then showed that this novel antibody has the potential to neutralise dengue virus and prevent signs of disease.

Another important feature of this antibody is that it acts on a part of the virus that is not normally targeted by the normal human immune response. This is important as the antibody would not need to compete with but would instead augment the overall natural immune response against dengue virus.


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Journal Reference:

  1. Luke N. Robinson, Kannan Tharakaraman, Kirk J. Rowley, Vivian V. Costa, Kuan Rong Chan, Yee Hwa Wong, Li Ching Ong, Hwee Cheng Tan, Tyree Koch, David Cain, Rama Kirloskar, Karthik Viswanathan, Chong Wai Liew, Hamid Tissire, Boopathy Ramakrishnan, James R. Myette, Gregory J. Babcock, V. Sasisekharan, Sylvie Alonso, Jianzhu Chen, Julien Lescar, Zachary Shriver, Eng Eong Ooi, Ram Sasisekharan. Structure-Guided Design of an Anti-dengue Antibody Directed to a Non-immunodominant Epitope. Cell, 2015; DOI: 10.1016/j.cell.2015.06.057

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ResearchSEA. "Engineering potential treatment for all four dengue serotypes." ScienceDaily. ScienceDaily, 19 July 2015. <www.sciencedaily.com/releases/2015/07/150719124246.htm>.
ResearchSEA. (2015, July 19). Engineering potential treatment for all four dengue serotypes. ScienceDaily. Retrieved May 23, 2017 from www.sciencedaily.com/releases/2015/07/150719124246.htm
ResearchSEA. "Engineering potential treatment for all four dengue serotypes." ScienceDaily. www.sciencedaily.com/releases/2015/07/150719124246.htm (accessed May 23, 2017).

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