Neurosurgery Resident and Clinical Researcher MME Foundation Mansoura, Egypt
Disclosure(s):
Mahmoud M. Elsayed, MD: No financial relationships to disclose
Introduction: While CRISPR-Cas systems have revolutionized gene editing, emerging technologies offer new potential for increased precision, reduced off-target effects, and broader therapeutic applications. This systematic review explores next-generation gene-editing tools beyond CRISPR, such as base editors, prime editors, and novel nucleases, highlighting their advantages, limitations, and future prospects.
Methods: A systematic search of studies published from 2018 to 2023 was conducted to identify emerging gene-editing technologies. Studies were selected based on their focus on novel tools beyond CRISPR, including base editors (BE), prime editors (PE), zinc finger nucleases (ZFNs), and transcription activator-like effector nucleases (TALENs). Data on editing efficiency, precision, and off-target effects were extracted. Python and R were used for meta-analytic modeling to assess overall efficacy and compare these technologies with CRISPR-Cas systems.
Results: A total of 45 studies met the inclusion criteria, covering a wide range of applications from genetic disease correction to agricultural enhancements. Base editors showed an average precision of 94%, significantly higher than traditional CRISPR-Cas9 (80%), with minimal off-target effects ( < 1%). Prime editors demonstrated remarkable versatility, allowing for targeted insertions, deletions, and base substitutions, with an average success rate of 78%. ZFNs and TALENs, although less frequently used, exhibited high specificity (92%) but required complex protein engineering. Comparatively, base and prime editors displayed more user-friendly designs and scalability, particularly in therapeutic contexts.
Conclusion : Emerging gene-editing technologies, particularly base and prime editors, offer substantial improvements in precision and versatility over CRISPR systems. These tools represent the future of gene editing, with potential applications ranging from human therapeutics to environmental sustainability. However, further optimization is needed to address limitations such as delivery challenges and editing efficiency in larger genomes. Continued research will shape the next frontier of genome engineering.