Investigate NF1 related disease
Neurofibromatosis 1 (NF1) is one of the most prevalent genetic syndromes affecting 1:2600-1:3000 individuals. NF1 is caused by autosomal dominant mutations in the NF1 gene leading to over-activation of the RAS pathway and uncontrolled cellular growth and proliferation. Up to 20% of the NF1 patients develop malignant tumors by the age of 50. Treatment of these patients is extremely complex due to the involvement of many incurable tumor types. Since current therapeutic options are limited, there is a need to develop new treatments for NF1 patients. Novel tools, including the clustered regularly interspaced short palindromic repeats (CRISPR)/CAS-9 system, enable efficient mammalian genome editing and have created exceptional opportunities for gene therapy. This system can be utilized to replace small regions in a gene, in the presence of an intact copy on a homolog chromosome or in the presence of an ectopic complimentary DNA fragment. Recent efforts to use CRISPR/CAS9 together with DNA templates as a “cut and paste system” for repairing mutations in the human genome have shown encouraging results in some cases. However, the low efficiency of “pasting” the delivered template due to low levels of homologous recombination (HR) repair is still a major obstacle that limits the clinical use of this strategy. This is especially true in non-dividing neuronal cells.
We aim to:
(i) To develop new approaches to Increase the level of HR in non-dividing neuronal cells.
(ii) Improve NF1 mutant function.
(iii) Find synthetic lethal genes with NF1.