Gene Editing and Genotoxicity: Targeting the Off-Targets

Area of Science:

• Biotechnology
• Molecular Biology
• Genetics

Background:

• Gene editing technologies, including Zinc Finger Nucleases (ZFN), Transcription Activator-Like Effector Nucleases (TALEN), and CRISPR-associated systems (CRISPR-Cas), have advanced significantly.
• These tools enable precise DNA sequence modification in human somatic cells, including stem and progenitor cells, with increasing efficiency.

Purpose of the Study:

• To review current state-of-the-art methodologies for evaluating the safety and genotoxicity of gene editing technologies.
• To discuss approaches for predicting expected and unexpected modifications during gene editing.
• To identify techniques with sufficient accuracy and predictability for clinical application.

Main Methods:

• Survey of existing methodologies for assessing gene editing outcomes.
• Analysis of benefits and limitations of current safety and genotoxicity evaluation techniques.
• Discussion of predictive approaches for gene editing accuracy.

Main Results:

• Several methodologies exist to predict gene editing outcomes, addressing both intended and unintended modifications.
• Current techniques vary in their accuracy and predictability for clinical use.
• There is an ongoing need for advanced technologies to ensure safety.

Conclusions:

• Robust safety and genotoxicity assessment technologies are essential for the clinical implementation of gene editing.
• Further development is required to achieve the necessary accuracy and predictability for widespread gene therapy.
• The review highlights the current landscape and future directions in gene editing safety evaluation.