Aug 2026· Trends in Biotechnology· 0 citations· 82 references
Medicine
TL;DR
It is argued that as CRISPR biotechnologies advance beyond the relative simplicity of in vitro applications, the understanding must also evolve to address the challenges of optimizing “on-target” and “off-target” mutational activities across the diverse contexts in which they occur.
Abstract
Recent FDA-approved gene editing therapies illustrate not only the transformative potential of CRISPR biotechnologies in treating a broad range of diseases but also the spectrum of possible molecular variations CRISPR therapeutics can adopt. These include exagamglogene autotemcel, an ex vivo Cas9-mediated therapy for hemoglobinopathies, and kayjayguran abengcemeran, an in vivo therapy using a PAM-altered, base-editing Cas9 variant for an ultra-rare metabolic disorder. Together, these therapies underscore how far CRISPR has advanced beyond its original use as a tool in biological/biomedical research. Here, we argue that as CRISPR biotechnologies advance beyond the relative simplicity of in vitro applications, our understanding must also evolve to address the challenges of optimizing “on-target” and “off-target” mutational activities across the diverse contexts in which they occur.
Gene editing has enormous potential in biomedical fields, including cancer and personalized medicine. CRISPR-Cas9 is a gene-editing system in which the Cas9 enzyme, guided by RNA derived from short palindromic repeats, alters DNA sequences to inhibit oncogenes through base and prime editing, thereby suppressing tumor growth. Despite significant advancements in anticancer therapies, limitations such as off-target effects, ethical concerns, and challenges in targeted delivery restrict its potential clinical applications. In the present review, we explore the mechanisms of CRISPR-Cas9 gene editing, recent technological advancements, and prospects for cancer management. We also provide insights into strategies for precise delivery, improved targeting accuracy, and the regulatory considerations surrounding CRISPR-Cas9 for oncological applications. Additionally, this review examines the potential of CRISPR-Cas9 in personalized cancer therapy and discusses approaches to enhance tumor-specific targeting and facilitate clinical translation.
Nikhil Rawal, Shruti Batra, Tanu Sharma et al.· Current pharmaceutical desig...· 0 citations
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.
Cancer immunotherapy has shown significant promise in certain patient populations, but further advancements are needed to extend its benefits to a wider range of patients. Clustered regularly interspaced short palindromic repeats (CRISPR)-based editing has rapidly evolved in recent years, enabling its transition into direct therapeutic applications. This review summarizes recent progress in applying CRISPR systems in vivo for cancer immunotherapy, focusing on approaches that target cancer cells and the tumor microenvironment, as well as those that directly engineer immune cell populations themselves. Novel CRISPR editing platforms and strategies enabling multiplexed editing have also recently demonstrated promising impacts on driving antitumor immunity, however, the platforms investigated are still in the early stages and further investigation will be needed to robustly assess the potential for clinical translation. Future work can expand the array of therapeutic targets by incorporating data from functional genomics and must also carefully evaluate both editing modalities and delivery systems to optimize efficacy, safety, and scalability.
Cole W. Christopher, Xiaoyu Zhou· Frontiers in Immunology· 0 citations
How CRISPR-enabled functional genomics approaches can reveal unexpected cancer dependencies and resistance mechanisms is outlined, and emerging applications of CRISPR-based diagnostics in oncology that convert precise nucleic acid sequence recognition into rapid mutation detection are discussed.
S. Grigg, Carolyn Shembrey, M. Fareh et al.· Nature Reviews Clinical Onco...· 1 citation
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
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.
M. Rezaee, F. Izadi, Saeed Nobaharian et al.· Beni-Suef University Journal...· 0 citations
