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Team Discovers a Piece of the Puzzle for Individualized Cancer Therapy Via Gene Silencing

28.05.2010
In a major cancer-research breakthrough, researchers at the McGill University, Department of Biochemistry have discovered that a small segment of a protein that interacts with RNA can control the normal expression of genes – including those that are active in cancer. A video outlining the discovery is available at http://podcasts.mcgill.ca/pods/press/nagar.mp4

The research, published online on May 26, 2010 by the prestigious journal Nature, has important immediate applications for laboratory research and is another step toward the kind of individualized cancer therapies researchers are pursuing vigorously around the world.

Human cells need to produce the correct proteins at the right time and in the appropriate quantities to stay healthy. One of the key means by which cells achieve this control is by "RNA interference", a form of gene silencing where small pieces of RNA, called micro RNAs, obstruct the production of specific proteins by interacting with their genetic code. However, not any piece of RNA can do this. Dr. Bhushan Nagar and graduate student Filipp Frank, in collaboration with Dr. Nahum Sonenberg at McGill’s new Life Sciences Complex, used structural biology to unravel how a small segment in the Argonaute proteins, the key molecules of RNA interference, can select the correct micro RNAs.

In doing so, the team has discovered that Argonaute proteins can potentially be exploited to enhance gene silencing. “RNA interference could be used as a viable therapeutic approach for inhibiting specific genes that are aberrantly active in diseases such as cancer”, Nagar said. “We now have a handle on being able to rationally modify micro RNAs to make them more efficient and possibly into therapeutic drugs.”

While therapeutic applications are many years away, this new insight provides an avenue to specifically control the production of proteins, which in cancer cells for example, are abnormal.

“This is fantastic news,” said Dr. David Thomas, Chair of McGill’s Department of Biochemistry. “You’ve seen stories lately about how we may see the end of chemotherapy? Well, this is part of that path in developing genetically based therapies that can be tailored to individual patients’ particular illnesses. It’s a great step forward.”

The research received funding from the Canadian Institutes of Health Research, the Human Frontier’s Science Program and supported by the FRSQ Groupe de Recherche Axé sur la Structure des Protéines (GRASP).

On the Web
Video explaining this research: http://podcasts.mcgill.ca/pods/press/nagar.mp4
For broadcast-quality footage, please contact William Raillant-Clark – 514-398-2189 or william.raillant-clark@mcgill.ca

McGill Biochemistry: http://www.mcgill.ca/biochemistry/

Découverte d’une pièce du casse-tête de la thérapie personnalisée contre le cancer

Des membres du Département de biochimie de l’Université McGill ont effectué une percée significative en matière de recherche sur le cancer. Ils ont découvert qu’un petit segment d’une protéine qui interfère avec l’ARN peut contrôler l’expression normale de gènes, notamment les gènes actifs dans les cellules cancéreuses. Consultez la vidéo suivante à ce sujet (en anglais): http://podcasts.mcgill.ca/pods/press/nagar.mp4

Publiés en ligne le 26 mai 2010 par le prestigieux journal Nature, les travaux ont déjà ouvert la voie à d’importantes applications pour la recherche en laboratoire et constituent une autre étape vers le type de thérapies personnalisées contre le cancer que des spécialistes du monde entier tentent ardemment de mettre au point.

Pour demeurer saine, la cellule humaine doit produire les bonnes protéines au bon moment, et ce, en quantité appropriée. Elle y parvient notamment grâce à l’ARN interférence, une forme de dégradation génétique par laquelle de petits morceaux d’ARN, appelés ARNm, bloquent la production de protéines spécifiques en interférant avec leur code génétique. Toutefois, tous les ARNm ne peuvent accomplir cette tâche. En collaboration avec le professeur Nahum Sonenberg du nouveau Complexe des sciences de la vie de McGill, le professeur Bhushan Nagar et l’étudiant aux cycles supérieurs Filipp Frank ont fait appel à la biologie structurelle pour mettre au jour un petit segment de protéines Argonaute - molécules essentielles à l’ARN interférence – apte à sélectionner les ARNm adéquats.

Ce faisant, l’équipe a découvert que les protéines Argonaute pouvaient éventuellement être exploitées pour amplifier la dégradation. « L’ARN interférence peut servir de démarche thérapeutique viable pour inhiber des gènes spécifiques exagérément actifs dans des cas de maladies comme le cancer », a déclaré le professeur Nagar. « Nous avons maintenant une porte ouverte sur la capacité de modifier rationnellement les ARNm pour les rendre plus efficaces, voire les transformer en médicaments. »

Même si l’on ne peut envisager d’applications thérapeutiques avant plusieurs années, ces nouvelles connaissances offrent une avenue pour réguler la production spécifique de protéines anormales, notamment dans les cellules cancéreuses.

« C’est une nouvelle formidable », a déclaré le professeur David Thomas, directeur du Département de biochimie de l’Université McGill. « Récemment, des reportages évoquant la fin de l’utilisation de la chimiothérapie ont été présentés. Eh bien, cela fait partie de ce parcours menant à la mise au point de thérapies fondées sur les gènes et personnalisées en fonction de la maladie à traiter. C’est un grand pas en avant. »

Financée par les Instituts de recherche en santé du Canada et le programme scientifique des frontières de l’humain, la recherche a été soutenue par le Groupe de recherche axé sur la structure des protéines du Fonds de la recherche en santé du Québec.

Internet : http://www.mcgill.ca/biochemistry/
Vidéo explicative : http://podcasts.mcgill.ca/pods/press/nagar.mp4

William Raillant-Clark | Newswise Science News
Further information:
http://www.mcgill.ca

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