Jul 2026· Theoretical and Natural Science· 0 citations
TL;DR
This review systematically summarizes the developmental logic, core mechanisms, clinical applications, advantages and limitations of the three generations of CRISPR-Cas technology in monogenic disorders, and analyzes the key challenges such as delivery efficiency, long-term safety, and treatment accessibility.
Abstract
CRISPR-Cas technology has undergone three generations of iterative evolution and has become the core strategy for the treatment of monogenic disorders. The first-generation standard nucleases typified by Cas9 and Cas12a rely on double-strand breaks (DSB) to achieve gene disruption and reactivation, which have been successfully translated into clinical practice and led to the approval of the first CRISPR therapy exagamglogene autotemcel (exa-cel) for β-hemoglobinopathies. The second-generation tools including base editors and prime editors realize DSB-free precise DNA modification, providing solutions for point mutations and small fragment lesions, and have entered early clinical trials. The third-generation represented by Cas13 RNA editing and epigenome editing achieves reversible and controllable gene regulation without altering genomic DNA, which is suitable for neurodegenerative and epigenetic monogenic diseases. This review systematically summarizes the developmental logic, core mechanisms, clinical applications, advantages and limitations of the three generations of CRISPR-Cas technology in monogenic disorders, and analyzes the key challenges such as delivery efficiency, long-term safety, and treatment accessibility, as well as future directions including genome writing and AI-driven optimization. It aims to provide a reference for the further clinical translation of CRISPR-based gene therapy for monogenic diseases.
The potential application of CRISPR technology for the possible management of geneticbased conditions, including sickle-cell anemia, β-thalassemia, cystic fibrosis, and Duchenne muscular dystrophy is described.
M. Veer, Poonam Nikam, Omkar More et al.· International Journal of Dru...· 0 citations
CRISPR-Cas9 gene editing technology has achieved milestone breakthroughs in the treatment of monogenic hereditary diseases. We systematically review the latest clinical research progress of this technology in treating common monogenic disorders, summarizing key efficacy data, safety outcomes, and current major obstacles. On this basis, we analyze the shift in application logic when extending from monogenic diseases to specific cancers and long COVID syndrome, that is, moving from defect repair to engineering modification and immunomodulation. For cancer, we discuss the prospects of CRISPR in CAR-T enhancement and oncogene disruption, as well as challenges such as tumor heterogeneity and delivery bottlenecks. For long COVID, we explore its value as a research tool and the prospects for direct therapy. Finally, we propose strategies to address common challenges including delivery optimization, off-target detection standardization, and ethical regulation. The success of CRISPR-Cas9 in monogenic diseases represents the prelude to precision medicine, whereas conquering complex diseases will require systematic leaps in target discovery, delivery technology, and safety profiles.
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
Over a decade of advances in Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) and CRISPR-associated protein 9 (Cas9)-based technologies have culminated in the first-ever FDA-approved CRISPR/Cas-based therapy. Aside from this approved therapy for sickle cell anemia, several CRISPR/Cas-based therapies are currently under development or testing for a range of chronic diseases, including viral diseases like human immunodeficiency virus type 1 (HIV-1) infection, genetic diseases like familial hypercholesterolemia, and cancer. The success of these therapies hinges on the effective delivery of CRISPR/Cas9 components to target regions, efficient Cas endonuclease editing, repair profiles generated, and their resulting outcomes. Here, we discuss the factors that influence the generation of CRISPR/Cas9-generated repair edits, the overall profiles, and outcome prediction(s), as well as the analytical tools that have been developed to date. Finally, how this technology has been used towards a functional HIV-1 cure is discussed.
Samuel N. Effah, Shirley C. Barrera, Nahia Urturi Ortiz et al.· International Journal of Mol...· 0 citations
This article synthesizes contemporary advancements in CRISPR-mediated mammalian genome modification, detailing core mechanisms – such as guide RNA and the Cas9 endonuclease – alongside next-generation modalities, including base and prime editing.
Olga Aldoshina, Dmitriy Lazarev, E. Smirnova· Veterinariya, Zootekhniya i...· 0 citations
Gene therapy is evolving from gene addition to precise genome editing, enabling the direct correction of disease-causing mutations. Breakthrough technologies, such as clustered regularly interspaced short palindromic repeats-CRISPR-associated protein (CRISPR-Cas) nucleases, base editors, prime editors, and CRISPR-associated transposases are reshaping the therapeutic landscape. This review covers the progression of precision editing technologies and their clinical applications, spanning from ex vivo therapies to in vivo treatments targeting vital organs. The rise of personalized medicine, highlighted by therapies, such as carbamoyl phosphate synthetase 1 editing, underscores the shift toward N-of-1 medicine for rare diseases. Clinical trial progress, delivery and accessibility challenges, and the role of AI in optimizing editing tools and predicting outcomes are also discussed. These innovations are transforming genetic medicine, offering the promise of safer, more durable, and personalized cures.
Tongtong Cui, Bojin Li, Bingyu Cai et al.· Trends in Molecular Medicine· 0 citations