Friday, May 13 2022

PhD student Dennis Dogbey, of the Medical Biotechnology and Immunotherapy (MB&I) Research Unit of the Institute of Infectious Diseases and Molecular Medicine at the University of Cape Town (UCT), based at the Faculty of Health Sciences, recently received a 2021 Google PhD Africa Fellowship for Human- Computer Interactions – as this year’s only African grantee in this sub-field.

Viral vectors are molecular tools used by scientists to introduce genetic material into cells. They have been used successfully for the treatment of many hereditary diseases and hold great promise for the development of future cancer therapies. Although approximately four viral vector-based gene therapies have been approved for use in patients, with several hundred currently being tested in clinical trials, various technological hurdles must be overcome to realize the full extent of their clinical impact.

One of the major bottlenecks with the use of viral vectors, particularly in the context of cancer gene therapy, is how to selectively deliver these vectors to target tissues and organs in the body. Due to their relatively small size and natural ability to transfer genetic material between cells in more than one tissue, targeted systemic delivery of viral vectors to distant organs is currently impossible.

“Our goal is to integrate commonly used viral vectors to develop a targeted drug delivery system, based on an innovative and knowledge-driven approach. “

In Dogbey’s project, the surface of viral vectors will be decorated with disease-specific antibodies using advanced computer and protein engineering methods. This new approach will allow the selective delivery of viral vectors to identified diseased cell populations. When used for cancer gene therapy, these viral vectors will allow the targeted delivery of toxic anticancer genes into tumor cells without damaging normal cells.

Dogbey explained: “Certain types of cancer continue to be a significant burden – particularly in Africa, where treatment is carried out through conventional strategies like chemotherapy, surgery and radiation. These often cause serious negative effects. and can make the patient resistant to treatment.

“Our goal is to integrate commonly used viral vectors to develop a targeted drug delivery system, based on an innovative and knowledge-driven approach. “

MB&I opens a new line of research

The Google Stock Exchange is offered in Africa, Australia, Canada, East Asia, Europe, India, New Zealand, South East Asia, and the United States. Five other scholarships were awarded in Africa in different sub-fields.

According to the mandate of the scholarship, the award is designed to directly support graduate students in the pursuit of their doctorate, as well as to connect them with a Google search mentor to nurture and maintain strong relationships with the academic community. The scholarship was established to recognize outstanding graduate students conducting cutting-edge and innovative research in fields relevant to IT and related fields, who also have the ambition to influence the future of technology.

“This Google Fellowship is the kind of support we desperately need to highlight the power of interdisciplinary collaborations.”

“This Google Fellowship is the kind of support we desperately need to demonstrate the power of interdisciplinary collaborations between computer simulation and applied research, especially in the area of ​​knowledge-based innovation in medical biotechnology,” said Professor Stefan Barth, who created the MB&I research unit.

“This type of assessment allows us to expand our activities into two main research areas illustrated by a) the use of supercomputer simulation of dynamic protein interactions to design next-generation recombinant immunotherapies, as illustrated in Conception du sniper: improvement of human cytolytic fusion proteins targeted for anticancer therapy via molecular simulation an article resulting from a collaboration between Prof. Barth and Prof. Paolo Carloni, director of the Institute for Advanced Simulation, FZ Jülich Germany, and (b) using bioinformatics big data interpretation tools to identify disease-specific biomarkers for precision, immunodiagnosis and medicine-focused therapy, ”added Professor Barth, who received a research chair. South African Level 1 in Cancer Biotechnology in 2015, which subsequently became n an integral part of the Integrative Biomedical Sciences Department at UCT. Barth has 25 years of experience in recombinant antibody technologies and creating knowledge-based innovations in the field of medical biotechnology.

He added: “This opens up a new line of research, in which we use the basic knowledge accumulated on antibody engineering to contribute to targeted gene therapy approaches. The future impact is highly dependent on a successful proof of concept of Dennis Work practice. “

Going forward, the main goal of the scholarship is to intensify the work Dogbey is doing in the lab.

Innovations to improve gene therapy

MB&I aims to provide the best possible scientific content and working environment in a setting with limited resources – which is the case in Africa. The quality of the research produced by the research unit is documented by the theses of the graduate students. This provides a solid basis for the continuation of this research work, contributing to the innovative engineering of proteins to provide next-generation diagnostics and therapies.

“After several years of work, we have since demonstrated the first proof of concept studies for our recombinant antibody approaches.”

Referring to the role of the research unit’s work, Dogbey said: “The MB&I is known for its innovative knowledge-driven research results – some of which have obtained international patents. It was a case of ideas meeting ideas. As early as 2016, Dr Olusiji Alex Akinrinmade – then a doctoral student, under the supervision of Professor Barth – began working on targeted viral vectors. Apart from these, ongoing studies in advanced countries have attempted to develop targeted viral vectors to improve gene therapy. A few publications from technologically advanced countries attest to this. “

Dr Akinrinmade, postdoctoral fellow at MB&I, said that when admitted as a first doctoral student by Barth, he was encouraged to establish targeted delivery of viral vectors using the platform technologies available at the Research Unit. “After several years of work, we have since demonstrated the first proof-of-concept studies for our recombinant antibody approaches. We now have the technical know-how to achieve our main objectives.”

Confident that the results of this work will contribute significantly to healthcare by addressing an unmet medical need in the field of gene therapy, Akinrinmade explained: The results of this project will provide stakeholders with the technical know-how to prepare the delivery shipments of new generation targeted genes. “

According to Dogbey, this line of research is particularly difficult due to several shortcomings associated with the modification of most viral vectors. For example, previous work has shown that the biology of most viral vectors can easily be compromised by the insertion of foreign structural sequences into the viral genome. In other cases, modification of viral vectors with antibodies can result in very low viral titers (yields) during production, resulting in insufficient amounts for preclinical or clinical testing.

“The deliverables for this project will include a portfolio of antibody-based targeted gene delivery vectors designed to impact the cancer gene therapy landscape,” Dogbey said.

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