Aug 2026· Beni-Suef University Journal of Basic and Applied Sciences· Vol 15· 0 citations· 150 references
TL;DR
A major focus of this review is the inclusion of recent hybrid systems (VLPs, SORT-LNPs) and the recognition that chemical modification of guide RNAs is a critical parameter for therapeutic success and that hybrid systems and stimuli-responsive nanoparticles are poised to dominate the next 5 years of clinical development.
Abstract
CRISPR/Cas9 has revolutionized genetic engineering since its repurposing as a programmable nuclease in 2012, yet its clinical translation remains fundamentally constrained by delivery barriers rather than editing efficiency. The system operates through acquisition, biogenesis, and interference mechanisms, but therapeutic application necessitates overcoming delivery challenges that are highly context-dependent. This review moves beyond a descriptive summary of 67 studies to provide a critical, barrier-focused analysis of delivery strategies. Our re-analysis of the tabulated data identifies quantitative trends across viral, non-viral, and physical platforms, evaluates trade-offs between efficiency and safety, and proposes a decision framework for vehicle selection based on target tissue and cargo type. A major focus of this review is the inclusion of recent hybrid systems (VLPs, SORT-LNPs) and the recognition that chemical modification of guide RNAs is a critical parameter for therapeutic success. A key forward-looking insight is that hybrid systems and stimuli-responsive nanoparticles are poised to dominate the next 5 years of clinical development, particularly for liver, CNS, and hematopoietic targets. Successful clinical translation of CRISPR/Cas9 will depend on context-specific delivery strategies that balance editing efficiency, safety, and clinical scalability.
The continued convergence of nanotechnology and genome engineering may support the development of personalized medicine strategies that adapt genetic engineering tools for patient-specific applications, thereby improving the safety and reliability of gene-editing therapies.
Raheem Mais, Ayush Kumar, Armand Ahmetaj et al.· International Journal of Mol...· 0 citations
This article aims to provide a working framework for verifying the potency, genomic integrity, and clinical safety of vector-based gene therapies—one intended to be useful both to laboratories developing these products and to those responsible for regulating them.
Yusra A. Radeef, Z. Abdullah, Eman Fadhel Abbas Awadh· International Journal of Mul...· 0 citations
This review critically evaluates CRISPR's role in RNA editing, emphasizing its importance for functional genomics and development of recombinant vaccines, andTranslational challenges are critically discussed, including off-target effects, delivery limitations, and ethical issues.
Mahmood Ul Hasan, M. Azhar, Noor-Ul-Saba et al.· Journal of Virological Metho...· 0 citations
This review summarises the current strategies of nanoparticle-mediated CRISPR-Cas9 delivery, including lipid, polymeric, hybrid, inorganic, and biomimetic nanoparticles.
Shouvik Mondal, Kriti Kumari· Advanced International Journ...· 0 citations
CRISPR has emerged as a next-generation gene-editing tool with the potential to target the molecular pathways associated with ageing and related disorders. It functions through RNA-guided Cas nucleases, directing DNA cleavage and utilizing the native DNA repair machinery for genetic manipulations. Advances in CRISPR technology have significantly enhanced the precision and flexibility of techniques for genome editing. The enzyme Cas9's ability to cut DNA at exact site has revolutionized genome editing by enabling accurate modifications within living eukaryotic cells. This review critically examines recent developments in CRISPR-based technologies, including Cas9, Cas12, base editing, prime editing, and CRISPR-mediated gene regulation. It highlights their rising applications in ageing research, with more emphasis on neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. The review also discusses the major pharmacological and translational challenges that currently limit clinical applications, including inefficient tissue-specific delivery, off-target genome editing, immunogenicity, manufacturing complexity, and long-term safety concerns. Also, recent progress in both, viral and non-viral delivery methods are critically evaluated, including adeno-associated viruses, lentivirus vectors, lipid nanoparticles, gold nanoparticles, exosomes, electroporation, and microinjection, is thoroughly discussed to highlight their therapeutic potential and translational limitations. Current studies indicate that CRISPR-based approaches have preclinical potential for targeting important hallmarks of ageing, particularly genomic instability, telomere attrition, and mitochondrial dysfunction. Other hallmarks of ageing, such as stem cell exhaustion, epigenetic modifications, and microbiome changes, are at earlier stages of development. Overall, this review describes future strategies for developing safe, precise, and clinically translatable CRISPR-based treatments to promote healthy ageing.
Sakshi Rathore, Akash Gupta, Kamal Shah et al.· Ageing Research Reviews· 0 citations
This review focuses on analytical and translational frameworks for CRISPR fidelity assessment, with emphasis on the strengths and limitations of current bioanalytical platforms.
Arpita Mukherjee· Journal of Rare Diseases· 1 citation