New 'molecular scissors' even more accurate than CRISPR-Cas9
Doing better than CRISPR-Cas9 is the bet of a team of researchers in biochemistry and molecular biophysics at Columbia University in the United States. On December 18, they published a study in the journal Nature, in which they revealed the operation and rendering of their new tool, called INTEGRATE.
It is based on the same principle as its predecessor CRISPR-Cas9: to target a specific area of DNA - genetic material - of a cell and to replace another fragment of DNA containing other genetic information.
No breakage of the DNA strand
But the means to achieve this differ between these two 'molecular scissors'. For the first, the Cas9 enzyme cuts the strand of DNA to be modified, the replacement fragment is introduced and then the machinery of the cell itself will come into play to repair the integrity of the DNA strand.
In the case of INTEGRATE, the principle is based on a seamless insertion of DNA strands, which reduces the risk of error during repair and increases the accuracy of genetic modification. The goal: to avoid, as with CRISPR-Cas9, unintentionally modifying genes other than the one initially targeted.
A mechanism borrowed from cholera bacteria
Indeed, American researchers use in their TOOL INTEGRATE a completely different system: the gene "jumper" of the bacterium Vibrio cholerae known to be responsible for cholera. It is this gene that has the peculiarity of being able to slide without breaking a new sequence in a strand of DNA.
The INTEGRATE complex borrowed from the bacterium Vibrio cholerae is therefore both able to recognize the DNA sequence on which to attach and to slip the genetic information it carries.
Targeting human genes in the long term
"We showed in our first study how to leverage INTEGRATE for targeted DNA insertions into bacterial cells," said Professor Sam Sternberg, co-author of the study, in a news release from Columbia University.
The next step for researchers is to further explore the tool they have developed to use it on humans to treat genetic diseases.
It is based on the same principle as its predecessor CRISPR-Cas9: to target a specific area of DNA - genetic material - of a cell and to replace another fragment of DNA containing other genetic information.
No breakage of the DNA strand
But the means to achieve this differ between these two 'molecular scissors'. For the first, the Cas9 enzyme cuts the strand of DNA to be modified, the replacement fragment is introduced and then the machinery of the cell itself will come into play to repair the integrity of the DNA strand.
In the case of INTEGRATE, the principle is based on a seamless insertion of DNA strands, which reduces the risk of error during repair and increases the accuracy of genetic modification. The goal: to avoid, as with CRISPR-Cas9, unintentionally modifying genes other than the one initially targeted.
A mechanism borrowed from cholera bacteria
Indeed, American researchers use in their TOOL INTEGRATE a completely different system: the gene "jumper" of the bacterium Vibrio cholerae known to be responsible for cholera. It is this gene that has the peculiarity of being able to slide without breaking a new sequence in a strand of DNA.
The INTEGRATE complex borrowed from the bacterium Vibrio cholerae is therefore both able to recognize the DNA sequence on which to attach and to slip the genetic information it carries.
Targeting human genes in the long term
"We showed in our first study how to leverage INTEGRATE for targeted DNA insertions into bacterial cells," said Professor Sam Sternberg, co-author of the study, in a news release from Columbia University.
The next step for researchers is to further explore the tool they have developed to use it on humans to treat genetic diseases.