RITDM™ gene editing technology

Gene editing avoiding DNA damage and applicable for repeat treatments

Many gene editing technologies involve the creation of single stranded or double stranded DNA breaks and make use bacterial proteins. Such technologies can result in off-target DNA damage and also they can lead to immunological reactions.

At PeterBio we created a new technology that does not depend on the creation of DNA breaks and that avoids the usage of bacterial or viral components.

Our RITDM™ (Recombination Induced Template-driven DNA Modification) technology is an innovative way of gene-editing that mimic cellular processes in which single stranded genomic DNA is generated. One such opportunity was developed based on carefully studying nature’s way of DNA replication. We looked in particular at the enzyme that can open the DNA double-helix: helicase. Human cells contain a number of different helicases, some of which use a structure, called a “beta-wing”, that can insert itself in between the two strands of the DNA helix, thereby “opening” the DNA helix and exposing short stretches of single stranded DNA

Inspired by this observation, we have created special fusion proteins that combine a sequence specific DNA binding domain with a helicase beta-wing. These fusion proteins can bind very specifically to a place in the genome where we want to make a genetic change. When bound at the target site, they can open the DNA helix at that specific site. Then a second component of the RITDM system, a single stranded DNA modification template can bind to the exposed single stranded target site. Thus, a complementary correction template can bind. The cells own DNA mismatch repair processes can be used to generate daughter cells with the desired DNA change.

For our fusion proteins we combine human zinc finger arrays with a human helicase beta-wing. By using human protein fragments that are present in human cells, we aim to minimize immune reactions. Doing this gives us the potential to treat patients at multiple ages and stages. For severe diseases it can be beneficial to have a first treatment as early as possible, with follow-up treatments as needed.

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