Portal de Murcia
www.portaldemurcia.com
The team of researchers led by the Professor of the Gene Expression Laboratory of the Salk Institute of the USA and Professor of Developmental Biology at UCAM has observed, after testing the technique (SATI) in mice with progeria (premature aging), a rejuvenation in several tissues, including the skin and spleen, and an increase of 45% in its useful life, which transferred to humans would be more than a decade.
The advance has been published by the scientific journal Cell Research.
The team of scientists led by Dr. Juan Carlos Izpisua, professor in the Laboratory of Gene Expression of the Salk Institute and Professor of Development Biology at UCAM, has developed a new tool for gene editing, SATI (short for 'intercellular linearized Single Arm donor mediated intron-Targeting Integration), aimed at curing numerous diseases caused by genetic mutations.
The tools for editing genes in living organisms offer an opportunity to treat a large number of inherited diseases.
However, many of these existing tools currently do not have the capacity to select specific areas of DNA, and developing new efficient tools is very complicated, since the tissues of living organisms have many different cell types.
The new SATI gene editing tool, developed thanks to the cofinancing of UCAM, allows the mouse genome to be edited, selecting a wide range of mutations and cell types, and could be used to correct a variety of mutations, such as that produced by the Huntington's disease and premature aging syndrome or progeria.
"In this study we have shown that SATI is a very powerful tool for genome editing," explains Juan Carlos Izpisua, lead author of the article.
"SATI could be a key element in the development of effective strategies for the correction of many types of genetic mutations, and opens the door for the use of gene editing in the cure of a wide range of diseases."
The tools for DNA modification, especially the CRISPR-Cas9 system, are effective in dividing cells, such as those in the skin or intestine.
This team, led by Dr. Izpisua, has previously shown that its CRISPR-Cas9-based gene editing technology, called HITI, was efficient in both dividing and non-dividing cells.
There are regions of DNA, called coding agents, that have the information to produce proteins;
while there are other regions, called non-coding, which are the ones that mark the amount of each protein to be manufactured.
These non-coding regions constitute the vast majority of DNA (~ 98%) and regulate many of the cellular functions, including the activation and deactivation of genes, so they could be a very valuable target for future gene therapies.
"We sought to create a versatile tool that acts on these non-coding regions of DNA, which would not affect the specific function of the gene and would allow selecting a wide range of mutations and cell types," says Estrella Núñez, Vice Chancellor for Research at UCAM and collaborator of Dr. Izpisua.
"As proof of concept, we focus on a mouse model of premature aging caused by a mutation that is difficult to repair using the existing gene editing tools so far."
This new tool, called SATI, is an advance of HITI, which allows targeting and cutting in new areas of the genome, and works by inserting a correct copy of the problem gene in the non-coding region of DNA prior to mutation.
This new gene is integrated into the genome together with the mutated gene, through one of the DNA repair pathways, correcting the damaging effects of the original mutated gene, without running the risk associated with total gene replacement.
Researchers have tested the SATI tool in live mice with progeria, a disease caused by a mutation in the LMNA gene.
Both humans and mice with progeria show signs of premature aging, cardiac dysfunction and a very short lifespan due to the accumulation of a protein called progerin.
By using SATI, a normal copy of the LMNA gene was inserted into mice with progeria and a rejuvenation could be observed in several tissues, including the skin and spleen, together with an increase in the life of the animal (45% compared to untreated mice with progeria).
If we increase this increase to humans, it would be more than a decade.
Therefore, SATI represents the first in vivo gene correction tool that can recognize regions of non-coding DNA in multiple types of tissues.
Source: UCAM
Privacy policy
- Legal notice
- Cookies