Introduction: CRISPR-Cas9 has emerged as one of the most transformative tools in genetic engineering, raising considerable hopes for the treatment of genetic disorders. Its high precision, programmability, and capacity for targeted genome modification represent key advantages. Nonetheless, efficient delivery of CRISPR components into target cells and the mitigation of off-target effects remain critical challenges that must be addressed.
Methods: This review surveyed articles published between 2022 and 2025 in PubMed to summarize the latest scientific developments in the field. Particular attention was given to two advanced CRISPR-derived technologies—Base Editing and Prime Editing. Base editing enables single-nucleotide substitutions without generating double-strand breaks and encompasses two primary classes: cytosine base editors (CBEs) and adenine base editors (ABEs). By contrast, Prime Editing offers enhanced precision and the versatility to introduce a wider range of genomic alterations, demonstrating significant therapeutic potential in conditions such as phenylketonuria and alpha-1 antitrypsin deficiency.
Results: To overcome delivery-related challenges, multiple approaches have been explored, which fall into three broad categories: physical methods (e.g., electroporation), viral vectors (e.g., adeno-associated virus [AAV] and lentivirus), and non-viral systems (e.g., polymeric and lipid-based nanoparticles). Recent findings highlight AAV-based vectors and polymeric nanoparticles as particularly promising candidates for clinical translation.
Conclusion: Taken together, the integration of next-generation editing modalities with optimized delivery systems is poised to advance the development of safer and more effective gene therapies in the near future.
Keywords: CRISPR-Cas9, genome editing, Base Editing, gene delivery, nanoparticles.