Development of a CRISPR-Cas9 genomic editing platform for the treatment of orphan diseases associated with thoracic aortic aneurysms.

Aortic aneurysms represent a high-risk pathology for patients, frequently requiring highly complex surgery. It is clearly established that a significant proportion of thoracic aortic aneurysms are associated with a group of orphan diseases of genetic origin that affect the proteins that form the extracellular matrix in the circulatory system. Recent advances in genomic editing technologies have the potential to correct genetic defects in many inherited diseases in which one or a few mutations are primarily responsible for the phenotype. However, current models for assessing the efficacy and safety of these
However, current models for assessing the efficacy and safety of these technologies have a number of shortcomings. The cells that produce the extracellular matrix in the aorta have established protocols for culture and for the introduction of
and nucleic acids, and they form a simple tissue structure that can be studied in isolation without having to
isolated without resorting to animal models that may produce results that cannot be extrapolated to
results that cannot be extrapolated to human disease. Additionally, the mutations that cause the syndromes associated with thoracic aortic aneurysms are generally dominant and therefore heterozygous and allow repair by genomic editing using the normal allele as a template. For this reason, we propose to conduct an in vitro study to study the feasibility of correcting the genetic defects that cause these diseases from cell cultures and tissues obtained from patients and to determine the efficiency of custom-designed genomic editing tools and the
possibility of observing unwanted effects on the genome of the cells under study. The results of this study may contribute to the advancement of the implementation of genomic editing for the correction of hereditary defects.