2-2017-1077

Specific DNA editing of Apo-E4 gene, the main risk factor in Alzheimer disease

THE NEED 
The current approach to the development of treatment of Alzheimer's disease  (AD), which  is the most prevalent form of dementia of the elderly, has  not produce any clinically meaningful results. The most prevalent genetic risk factor of AD, with more than 50% of the patients, is the Apolipoprotein E4 (apoE4) gene. 
 
TECHNOLOGY
In principle the pathological effects of apoE4 could be counteracted at the gene or at the protein levels where the former has the advantage that once achieved the effects are permanent.  The discovery of the gene editing  CRISPR  technique enables the editing of genes by a precision previously unheard of. We have recently applied a this approach to the apoE4 gene. The problem is that the difference between ApoE4 and ApoE3 sequence is one amino acid. Therefore we added another extra proprietary technique (the use of a specific PAM sequence) in order to have the CRISPR distingwish between the ApoE4 which will be deleted and the ApoE3 that will not. To date we have shown in cell culture experiments that it can be used to specifically and effectively silence the apoE4 gene and its protein product. Currently the project is extend to the whole animal model of ApoE4/3 mice. 
 
POTENTIAL APPLICATION
Our novel technology might be used in individuals who have one apoE4 Allele (most of AD patients) to remove the ApoE4 gene thereby leaving the functional ApoE3 allele active.
 ADVANTAGES  The project is led by Prof Danny Michaeslon, a renowned expert in the AD apoE4 fields and Prof Dani Offen who is a leader and pioneer in gene therapy for neurodegenerative diseases and a co-founder of several biotechnology companies developing gene and cell therapies. 
 The use of the special PAM technique to ensure only ApoE4 is edited thereby presenting a potential Alzheimer's gene therapy approach. 

 
PATENTS 
A provisional patetnt was filed in March 2017