Genetic Vaccine · Study the therapeutic and preventive potential of targeting oncogenic mutations with CRISPR-Cas9 technology
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-04-01 → 2021-03-31
- EU contribution
- €160,932
- Participants
- 1
- Scheme
- MSCA-IF-EF-RI
Lines connect the coordinator with its partners.
Results in brief
Study the therapeutic and preventive potential of targeting oncogenic mutations with CRISPR-Cas9 technology
Lung cancer is the leading cause of death related to cancer in the world, accounting for 25.3% of all cancer deaths. Non-small cell lung cancer (NSCLC) comprises 85% of all lung cancers, and adenocarcinoma is the most represented type among them (40%). The majority of lung cancers are caused by the accumulation of genetic alterations and the genes that are mostly mutated are EGFR (epidermal growth factor receptor) and KRAS (Kirsten rat sarcoma viral oncogene). Mutations in KRAS occur more frequently in lung adenocarcinomas (approximately 25%). When the KRAS gene is mutated, the Ras protein gets constitutively active, resulting in continuous cell proliferation. Most mutations in KRAS (approximately 80%) are located in a particular residue of the protein, therefore, we seek to prevent or disrupt such mutations in order to impede carcinogenesis and/or damage an established tumor.
Data: CORDIS, © European Union
Project objective
Genome editing has enriched our understanding of mechanisms of the human pathology. Genome editing took a significant advance with the recent development of the CRISPR-Cas9 technology. CRISPR is an acronym for: Clustered Regularly Interspaced Short Palindromic Repeats and it is an adaptation of a prokaryotic functional system. It uses a single guide RNA to direct Cas9 activity to a specific part of the genome, therefore, this system can be used for gene editing and regulation.Cancer is a genetic disease where some DNA-damaged cells begin to divide without stopping and spread into surrounding tissues. Interestingly, in some tumors, there is a dependency of a single oncogenic activity (oncogene addiction). This phenomenon indicates that mutations in key oncogenes (driver mutation) are able to drive carcinogenesis and maintain the tumor phenotype. Suggestively, if we can prevent or disrupt these mutations, we can difficult carcinogenesis or damage an established tumoral phenotype. In this proposal, we seek out for using Crispr-Cas9 technology to target driver mutations and evaluate its therapeutic and preventive value. To develop a proof of concept, we will focus on lung cancer driven by KRAS mutations. The generating of a transgenic mouse expressing Crispr-Cas9 designed to target the mutation Kras C12C will allow us to test the potential cancer-resistant phenotype and raise the concept of Genetic Vaccines.
Original text from CORDIS.
Participants
- UNIVERSIDAD DE GRANADA · GranadaCoordinatorSpain
Links
Data: CORDIS, © European Union