New methods of gene therapy, more accurate and safer than CRISPR

(ORDO NEWS) — Scientists are developing more and more accurate and safe methods of editing the genome directly in a living organism.

The CRISPR-Cas method has become a huge breakthrough, but still it does not yet provide either sufficient reliability or patient safety. The error rate is still quite high. Geneticists develop new methods and improve already known ones.

Molecular scissors get sharper and more precise

Clinical trials have begun in which geneticists plan to test on a living patient whether it is safe to use a gene therapy method called the single nucleotide substitution method.

The scientists plan to use the insights from CRISPR-Cas9 technology to make precise single-letter (single-nucleotide) changes to the DNA sequence in a human cholesterol regulator.

This study will be followed by another, later this year, an attempt will be made to cure a patient suffering from sickle cell anemia, a genetic blood disease, using the same method.

New methods of gene therapy more accurate and safer than CRISPR 2
Genotyping and DNA sequencing

Single nucleotide substitution method

When editing the CRISPR–Cas9 genome, the Cas9 enzyme cuts both strands of DNA at the site that is to be edited. DNA repair processes in the cell sew the strands together again, but sometimes they make mistakes.

And this means that the sequence of nucleotides changes, which can lead to the fact that the gene (if the change was made to the genome) will stop working.

The method of single nucleotide substitutions itself was proposed in 2016 and has been constantly improved and refined.

With a single nucleotide substitution, the work is much more accurate than with CRISPR-Cas9. One enzyme cuts only one strand of the double helix, while another enzyme chemically converts one DNA letter into another.

This is a much more careful and precise intervention. It is best suited when only one nucleotide needs to be replaced for gene therapy. This is the case, for example, with sickle cell anemia.

The trials that have begun will use an editor that also needs to make just one substitution: convert adenine (A) to guanine (G) in the gene that codes for the PCSK9 protein, a key regulator of blood cholesterol levels.

How the editing went will be known immediately, but the real results will have to wait. But geneticists consider the method of single nucleotide substitutions promising.

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