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.
Abstract
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.
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 Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology is a cutting-edge genome editing tool based on the adaptive immune mechanism of prokaryotes. This system, which operates through three key stages‒adaptation, expression, and interference‒offers high precision and efficiency in genetic modification. This article explores the mechanisms of CRISPR/Cas action and its applications in hematologic malignancies, breast cancer, colorectal cancer, gastric cancer, and lung cancer. Genome editing has demonstrated significant effectiveness in suppressing tumor growth, enhancing cellular sensitivity to therapy, and developing personalized treatment approaches. CRISPR/Cas enhances the efficacy of Chimeric Antigen Receptor T-cell Therapy (CAR-T) and helps overcome tumor cell resistance to treatment. The technology is also actively utilized in genetic screening to identify gene functions and discover new therapeutic targets. However, several challenges remain, including off-target effects, immune responses, and difficulties in delivering CRISPR components to target cells. This article discusses promising strategies to overcome these limitations, such as the development of novel Cas protein variants, improved delivery methods, and epigenetic approaches. CRISPR/Cas represents one of the most promising tools in molecular biology, providing the ability to precisely investigate gene functions and to develop new experimental strategies for therapeutic intervention. The potential of this technology is defined by its flexibility and applicability across a wide range of tasks‒including target validation, disease modeling, and the generation of advanced cellular products. However, its full integration into clinical practice requires further studies aimed at improving safety, reducing the frequency of unintended effects, and developing reliable delivery systems.
M. Omarov, E. Karacheva, M. M. Arapieva et al.· Сибирский научный медицински...· 0 citations
Overall, CRISPR/Cas9 represents a promising yet evolving platform in oncology, with its future clinical success dependent on achieving a balance between precision, safety, scalability, and long-term therapeutic durability.
C. Ng, Sakina Mustafa, X. Y. Yap et al.· Frontiers in Oncology· 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
A recent major breakthrough in cancer immunotherapy is the Chimeric antigen receptor-T cell (CAR-T cell) therapy, which has shown significant clinical efficacy in haematological malignancy treatment. Nonetheless, its application in a more general way is limited by a number of challenges, such as T-cell exhaustion, off-target associated toxicities, and the difficulty of personalised manufacturing. Recently, new opportunities have come into solving these problems with the introduction of clustered regularly interspaced short tandem repeats (CRISPR)-Cas9 genome editing, which has made it possible to perform precise and combinatorial genetic editing in CAR-T cells. The important applications of CRISPR in CAR-T cell engineering, which include the disruption of inhibitory immune checkpoints to enhance antitumour activity, the generation of universal allogeneic CAR-T cells by deletion of T-cell receptor and human leukocyte antigen (HLA) genes, and the modulation of cytokine signalling pathways to reduce toxicity are discussed in this review. Moreover, novel approaches, including targeted CAR integration and multiplex gene editing, are discussed as having the potential to enhance the therapeutic efficacy and scalability. In spite of these improvements, there are issues of off-target effect, delivery efficacy, genomic instability, and unaddressed issues of long-term safety. CAR-T cell therapies are likely to be improved further in future through advancements in genome editing technology, delivery methods, and synthetic biology. In general, CRISPR/Cas9-based engineering is a promising way of developing the next generation of precision cancer immunotherapy.
Meng-Ying Liu· International Journal of Bio...· 0 citations
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