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Genome Editing with CRISPR Technology

Dr. Ayal Hendel, of BIU’s Goodman Faculty of Life Sciences, and his partners, have developed an innovative software tool for evaluating and measuring errors that occur during CRISPR editing

תמונה
Ayal Hendel

Dr. Ayal Hendel, of BIU’s Goodman Faculty of Life Sciences, and his partners, have developed an innovative software tool for evaluating and measuring errors that occur during CRISPR editing

CRISPR technology enables precise editing of genomes, allowing for changes in DNA sequences that can alter gene function. Its applications range from correcting genetic defects and treating diseases to improving agricultural crops.

Genome editing tools, such as CRISPR-Cas9 technology, can be engineered to make precise changes to a target chromosome where a particular gene or functional element is located. However, CRISPR editing carries the risk of off-target activity, resulting in unintended genomic changes. To enhance the accuracy of CRISPR-Cas9 technology in medical practice, controlling off-target editing is crucial.

Existing measurement methods lack statistical estimates and sensitivity for experiments with low editing rates. They also require significant effort in identifying translocations.

In a breakthrough reported in the journal Nature Communication, a multidisciplinary team of researchers from Bar-Ilan University and the Interdisciplinary Center (IDC), Herzliya) has developed CRISPECTOR. This software tool locates, checks, and measures off-target editing activity, including negative translocation events that may lead to cancer. CRISPECTOR utilizes a standard assay, performing multiplexed PCR amplification and next-generation sequencing (NGS).

CRISPECTOR analyzes NGS data from CRISPR Cas9 experiments, employing statistical modelling to accurately determine and quantify off-target activity. It improves detection rates for weak but significant off-target activity and identifies negative translocation events during editing experiments.

Dr. Ayal Hendel emphasizes the importance of detecting low levels of off-target activity and negative translocation events, particularly in clinical applications. Early identification of these events is crucial for therapeutic protocols in gene therapy to prevent potential cancer development.

Collaborating with Prof. Zohar Yakhini of the Arazi School of Computer Science (IDC, Herzliya), Dr. Hendel's team successfully addressed the limitations of existing quantification tools through their research using CRISPR-Cas9 technology to edit genes related to blood and immune system disorders.

Prof. Zohar Yakhini highlights that CRISPECTOR overcomes background noise in deep tiling experiments, enabling the identification and quantification of low levels of off-target activity and negative translocation events. This tool ensures safer clinical use of genome editing and expands the detection range of genomic aberrations.

Dr.  Hendel’s laboratory and Yakhini's research group intend to apply CRISPECTOR in potential treatments for immune system genetic disorders and cancer immunotherapy approaches.

This collaborative research project received support from the European Research Council (ERC) under the Horizon 2020 program, as well as from the Adams program of the Israel Academy of Sciences and Humanities.

Dr. Ayal Hendel is among the organizers of the 2023 Meeting of Israeli Society of Gene and Cell Therapy (ISGCT) which will take place on July 3, 2023 at Bar-Ilan University in Ramat Gan.

“In our upcoming ISGCT 2023 meeting, we are thrilled to have Professor Matthew Porteus from Stanford University as the keynote speaker. We are also excited about the impressive line-up of speakers from Israeli academia, clinics, and industry. Please join us at the ISGCT 2023 meeting.”

Register here.