Algentech’s invention optimizes the cellular process known as homologous recombination. In order to precisely insert or modify a genetic sequence, existing technologies use nucleases that introduce specific breaks in the target DNA and then rely on the cellular machinery to complete the editing process. The mechanism is simple: the DNA fragment (donor DNA) carrying the genetic modification or sequence to be inserted has at its ends sequences homologous to the DNA strand to be modified. This similarity around the cutting site is recognized by the cellular machinery: the strands assemble. The natural DNA repair process then repairs the cut zone, using the donor DNA fragment as a matrix, inserting it into the target DNA. However, the effectiveness of homologous recombination repair remains low.
ALGENTECH’s invention significantly increases the efficiency of the homologous recombination process by producing two modules:
- a multi-domain protein capable of binding to the fragment to be inserted and to the target DNA;
- a donor DNA amplification vector that relies on a viral replication system. The technique produces a large amount of donor DNA strands, thus multiplying the efficiency of modifications introduced: a technological leap that finds applications in crop improvement, gene therapy and synthetic biology.
“The issuance of this patent in the United States in the field of nuclear genome editing is a major step in our strategy and strengthens our intellectual property portfolio in a sector that has revolutionized genomics in recent years,” says Alexander Sorokin, President of Algentech.
The figure on the left: The double –stranded breaks induced on the genome by nucleases are repaired by a homologous recombination mechanism that occurs between genomic DNA and donor DNA
The figure on the right: A large number of donor DNA molecules are produced by Algentech’s patented replication system (REP), thus contributing to the effectiveness of homologous recombination.