Among the initiatives launched at the closing of the France-Singapore Year of Innovation in March 2019, the Embassy of France, in partnership with the National Research Foundation (NRF) and the Collège de France, and with the support of the PSL University, decided to organise the France-Singapore Science and Innovation Lecture Series.
This initiative was launched on 29 October 2019 with the inaugural lecture by Prof Philippe Sansonetti, Professor at the Collège de France and a researcher in microbiology and infectious diseases at the Pasteur Institute. This conference was organised by the Department of Microbiology and Immunology and the Life Sciences Institute of the National University of Singapore, in the framework of the Voilah! France Singapore Festival and with the support of French Lab Singapore.
The second lecture in the series was given by Prof Alain Fischer, Professor of pediatric immunology and Chair of Experimental Medicine at the Collège de France on 16 January 2020 at the Duke-NUS Medical School.
While in Singapore, Prof Fischer also gave a plenary lecture at the the Global Young Scientists Summit (GYSS) and was a panelist on its forum, “The Future of Medicine”. The annual GYSS provides a global platform for conversations on science and research, technology innovation and society, and solutions to global challenges between young and upcoming researchers and eminent scientists and technology leaders.
The conference was a great success and attracted more than 130 participants.
Prof Alain Fischer’s lifelong work focused on the immune deficiencies present at birth and the curative approaches using gene therapy. In 1999, he achieved the world’s first clinical successes in gene therapy for a dozen bubble children (whose immune defenses were severely weakened or even non-existent). He is now considered a pioneer in this field and has received many awards such as the Grand Prix INSERM.
The immune system is made up of a myriad of components that play key roles in the control of autoimmune infectious diseases, allergies and cancer. The discovery over the last 30 years of more than 400 inherited diseases of the immune system has contributed to the deciphering of key mechanisms of immune responses and to the clinical development of gene therapy techniques.
These techniques aim to correct an inherited disease caused by a gene mutation through the delivery of a functional copy of the gene into cells. This idea emerged in the 1970s when it became possible to use modified viruses as carriers of the gene sequence of therapeutic interest. By bringing this functional gene into the cell, it is now possible to modify the expression of the mutated gene, add a new gene to create a new function or even correct the mutation itself.
To make a gene therapy effective, the functional gene in question and using a vector (virus carrying the gene) must be added to the gene of interest. The challenges faced are complex, which explains the slow development of this approach: it is necessary to target the relevant cell, obtain an adequate level of expression (neither too much nor too little) of the gene of interest, avoid a toxic effect and an immune reaction against the vector.
Two strategies are globally used, based on vectors that allow the integration of the gene of interest inside the cell genome and thus its replication at each cell division, and on the persistence of the gene of interest without integration, which avoids any risk of genotoxicity.
Two types of vectors are used: the first is represented by retroviruses for which RNA after retrotranscription into DNA integrates into the cellular genome. The second is essentially represented by adeno associated viruses (AAVs) which penetrate all cells and whose genetic material can persist in an episomal state (a type of DNA).
The presentation has been mainly focused on the first type of vector. Cells, once corrected ex vivo, can lead to normal lymphocytes in vivo, called T-cell precursor. In early clinical trials, some patients were observed to have developed leukemia, which would have caused the death of one of six people suffering from the cancer.
Studies conducted since 2005 have made it possible not only to reduce the toxic effects, but also to perfect the technique by having better control of parameters such as the transduction (expansion) capacity of the T-cell including the expression of the active gene. These studies have now led to safe and efficacious usage for three diseases, while further extension is being considered to treat more genetic diseases of the hematopoietic system, i.e. the building of blood and the immune system.
The third lecture of the 2019-2020 France-Singapore Science and Innovation Lecture Series will be given in June 2020 by Prof Pierre-Michel Menger, Professor at the Collège de France who is a prominent sociologist specialising in “creative work” and value creation through innovation.