Description of the project and research questions being asked

Recently, researchers have identified a new class of proteins called Tal effector (TALE). These proteins attached to a specific DNA sequence (a series of nucleotides). The code permitting this specific attachment has been recently broken and it is now possible to make new TALE proteins that attach to a desired DNA sequence. The attachment of a TALE to the regulator DNA sequence (promoter of a gene) permits to induce its expression. These new TALE proteins are thus a new type of reagents (drugs) to treat hereditary diseases by inducing the expression of a specific gene that has beneficial effect. We have already good preliminary results for Friedreich ataxia, a disease due to the production of an insufficient amount of a mitochondrial protein called frataxin. The same TALE technology could be used to treat Sickle-cell anemia http://en.wikipedia.org/wiki/Sickle-cell_disease. This hereditary disease is due to a mutation in the hemoglobin B gene resulting in abnormal hemoglobin B protein and abnormal shape and function of the red blood cells.

 Some experimental results indicated that (expression) synthesis of the fetal hemoglobin (gamma) in patients with sickle-cell disease prevents the development of the disease. The aim of our research project is thus to develop a treatment based of producing a new TALE protein that would specifically attach to the promoter and increase the synthesis of the fetal hemoglobin. Other TALE proteins could eventually be developed to induce the expression of other genes to treat other hereditary diseases.

Why this matters and should be exciting to backers

During the lasts 20 years, the genes responsible for 7000 different hereditary diseases have been identified. However, very little progress has been done towards the development of therapies. In the last 3 years, a new class of proteins called TALEs that attach specifically to a desired DNA sequence (of nucleotides) have been identified. It is now possible to make in a few days a new TALE protein that attach to DNA (a nucleotide) sequence within the regulator region (promoter of a gene). This possibility offers a new method to treat several hereditary diseases by inducing the synthesis (expression) of a protein, which compensate for the absence, the reduced expression or the presence of a mutated protein in patients affected by an hereditary disease. Our research project may open the way to treat several other hereditary diseases for which there are currently no treatment. We have targeted Sickle-cell anemia because it is a disease frequent in the black population particularly in Congo where the disease affects 1 person out of 100. This high frequency results in an important familial and social problem in this country.

What your money can do

The money raised on the Petridish web site will be used by our research group to do the initial experiments. We will design 12 new TALE proteins that can attach to different nucleotide sequences within the promoter of the hemoglobin gamma chain. We will then verify whether these TALEs can increase the expression of this protein in precursors of the red blood cells. This is the first step towards the development of a therapy based on the use of specific TALE proteins. These results will then be used to apply for a 3 years grant of roughly $150,000. Per year from the Canadian Institute of Health Research to do animal experiments with a mouse model of the disease. Such animal experiments are required to be able to eventually have the permission to do a formal Phase I clinical trial in Sickel-cell patients. 

Potential discoveries

Our research project will hopefully lead to the development of a treatment for Sickle-cell anemia. Moreover, a similar therapeutic approach could be used for other hereditary diseases for which there are currently no treatment.

Biography

I am a full university professor in the Department of Molecular Medicine at Laval University (Quebec, Canada). I have been doing research to develop treatments for hereditary diseases for 25 years. Focusing on Duchenne Muscular Dystrophy and more recently on Friedreich ataxia. I have published over 225 scientific articles on the results of my research and trained more than 50 graduated students. However, I currently have 2 new graduated students from Congo that have told me that Sickle-cell anemia is a very severe disease in their country and with their help and your help I would like to start a new research project to develop a treatment