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Pharmacogenomics and CRISPR-based therapies.
Pharmacogenomics and CRISPR-based treatments are two areas of precision medicine that are advancing together. Pharmacogenomics involves studying how differences in someone's genes can change the effect of medications on them. Pharmacogenomics helps reduce adverse reactions to drugs and improve healing by choosing and measuring drugs according to a patient's genetic information. Additionally, CRISPR-Cas systems now serve as leading genome editing tools that allow precise alterations at given points of the genome. CRISPR technology's use in pharmacogenomics creates new opportunities for modifying gene expression, fixing harmful mutations, and creating innovative treatment approaches. A more proactive approach to illness treatment is supported by this synergy, in which genetic factors serve as both direct targets for intervention and a basis for medication selection. This chapter examines the theoretical and practical frameworks that link CRISPR-based treatments with pharmacogenomics, emphasizing recent uses in pharmacoresistance, cancer, and monogenic diseases. To guarantee safe and fair deployment, it also covers the ethical, legal, and technical issues that need to be resolved. When combined, these technologies hold the potential to revolutionize medicine by facilitating individualized and curative drugs.
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Emerging DNA & RNA editing strategies for the treatment of epidermolysis bullosa.
Background: Epidermolysis bullosa (EB) is a clinically-heterogeneous genodermatosis with severe manifestations in the skin and other organs. The significant burden this condition places on patients justifies the development of gene therapeutic strategies targeting the genetic cause of the disease. Methods: Emerging RNA and DNA editing tools have shown remarkable advances in efficiency and safety. Applicable both in ex vivo- and in vivo settings, these gene therapeutics based on gene replacement or editing are either at the pre-clinical or clinical stage. Results: The recent landmark FDA approvals for gene editing based on CRISPR/Cas9, along with the first FDA-approved redosable in vivo gene replacement therapy for EB, will invigorate ongoing research efforts, increasing the likelihood of achieving local cure via CRISPR-based technologies in the near future. Conclusions: This review discusses the status quo of current gene therapeutics that act at the level of RNA or DNA, all with the common aim of improving the quality of life for EB patients.
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Application of genome-editing systems to enhance available pig resources for agriculture and biomedicine.
Traditionally, genetic engineering in the pig was a challenging task. Genetic engineering of somatic cells followed by somatic cell nuclear transfer (SCNT) could produce genetically engineered (GE) pigs carrying site-specific modifications. However, due to difficulties in engineering the genome of somatic cells and developmental defects associated with SCNT, a limited number of GE pig models were reported. Recent developments in genome-editing tools, such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) 9 system, have markedly changed the effort and time required to produce GE pig models. The frequency of genetic engineering in somatic cells is now practical. In addition, SCNT is no longer essential in producing GE pigs carrying site-specific modifications, because direct injection of genome-editing systems into developing embryos introduces targeted modifications. To date, the CRISPR/Cas9 system is the most convenient, cost-effective, timely and commonly used genome-editing technology. Several applicable biomedical and agricultural pig models have been generated using the CRISPR/Cas9 system. Although the efficiency of genetic engineering has been markedly enhanced with the use of genome-editing systems, improvements are still needed to optimally use the emerging technology. Current and future advances in genome-editing strategies will have a monumental effect on pig models used in agriculture and biomedicine.
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A scoping review of gene editing in clinical trials: identifying aspects of trial design to accelerate clinical adoption.
BACKGROUND: Initial clinical trials of gene editing have recently emerged and generated significant interest in this promising therapy. A scoping review is needed to understand aspects of study design that may accelerate further clinical translation. METHODS: A systematic search of published clinical trials was conducted to May 22, 2025. RESULTS: Twenty-nine published trials were identified for analysis (420 patients; median ages 6 months to 90 years). The most common gene editing technology used was CRISPR-Cas9 (23 studies, 79%). Hematopoietic cells were targeted most frequently, and leukemias and lymphomas were the most common clinical indications (8 studies; 27.5%), followed by hemoglobin disorders (6; 20.6%), solid tumors (6; 20.6%), rare genetic diseases (5; 17.2%), and others (4; 13.8%). All trials were early-phase (Phase I/II) with only 1 controlled study (29 patients). Six studies used in vivo approaches while all others performed gene editing ex vivo. Gene transfection was by electroporation (9 studies; 31.0%), viral-mediated transfection (6; 20.7%), or by lipid nanoparticles (3; 10.3%). Commonly reported outcomes included early safety and adverse events, mortality, persistence of edited cells, clinical and functional responses. Studies of leukemia/lymphoma reported rates of complete remission in 15-92% while we identified important and sustained increases in mean hemoglobin levels in studies of hemoglobin disorders. Edited cells were detected in most studies at 3 and 6 months but later timepoints were reported less frequently. While early serious adverse events were infrequently observed, reporting of longer-term outcomes was lacking. CONCLUSION: Gene editing appears feasible and generally safe in humans although important safety outcomes such as long-term oncogenic surveillance outcomes remain to be addressed. A broad range of conditions have been treated, and most often leverages the CRISPR-Cas9 technology with transfection by electroporation. The persistence of edited cells remains ill-defined and longer-term safety outcomes are needed. Studies optimizing CART therapy for leukemia/lymphoma and treatment of hemoglobin disorders appear poised for significant clinical adoption.
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Protocol for generating in-frame seamless knockins in Drosophila using the SEED/Harvest technology.
The generation of knockins is fundamental to dissect biological systems. SEED/Harvest, a technology based on CRISPR-Cas9, offers a powerful approach for seamless genome editing in Drosophila. Here, we present a protocol to tag any gene in the Drosophila genome using SEED/Harvest technology. We describe knockin design, plasmid preparation, injection, and insertion screening. We then detail procedures for germline harvesting. The technique combines straightforward cloning and robust screening of insertions, while still resulting in scarless gene editing. For complete details on the use and execution of this protocol, please refer to Aguilar et al.1.
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[Research progress of gene therapy in clinical application].
In the 1960s, scientists first raised the idea of curing genetic diseases using gene therapy. This new conceptual strategy aimed to achieve a much longer therapeutic effect by introducing exogenous genetic materials into the patients. After more than five decades of ups and downs, gene therapy has been brought into a new era by those milestone breakthroughs in the 21st century. Here we reviewed and summarized the history and breakthroughs of gene therapy, including some critical clinical trials, approved drugs, and emerging gene editing techniques. We believe that with their unique advantages over traditional therapies, more gene therapies will become practical approaches to genetic diseases and benefit the entire human race.
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Plant Tissue Culture: A Battle Horse in the Genome Editing Using CRISPR/Cas9.
Plant tissue culture (PTC) is a set of techniques for culturing cells, tissues, or organs in an aseptic medium with a defined chemical composition, in a controlled environment. Tissue culture, when combined with molecular biology techniques, becomes a powerful tool for the study of metabolic pathways, elucidation of cellular processes, genetic improvement and, through genetic engineering, the generation of cell lines resistant to biotic and abiotic stress, obtaining improved plants of agronomic interest, or studying the complex cellular genome. In this chapter, we analyze in general the use of plant tissue culture, in particular protoplasts and calli, in the implementation of CRISPR/Cas9 technology.
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CRISPR-based gene editing for antimicrobial resistance control in human medicine.
Antimicrobial resistance (AMR) has already become one of the most urgent threats to the public health of this century. In 2019 alone, it directly causes about 1.27 million deaths and it was estimated that 1.91 million people will die yearly by 2050 should present trends persist. The traditional antibiotic development pipelines have been shown to be structurally insufficient to meet the rate at which bacterial populations have developed, diversified and spread resistance determinants, typically by horizontal gene transfer. In this context, CRISPR-Cas gene editing has become a focused antimicrobial approach that can selectively target resistance genes, virulence factors, and mobile genetic elements without the broad-spectrum collateral damage associated with conventional antibiotics. The review assesses CRISPR-Cas systems, namely Cas9, Cas12a, Cas3, and Cas13 in the context of two complementary mechanistic strategies namely selective killing of pathogens and antibiotic resensitization by the targeted disruption of gene resistance. We compare the impact of key delivery systems, such as bacteriophage vectors, lipid nanoparticles, and conjugative plasmids, evaluating them based on their therapeutic activity, host selectivity, and possible translation. The present state of clinical translations is discussed, including the two most advanced clinical-stage candidates SNIPR001 (Phase I/II, NCT05277350) and LBP-EC01 (Phase 2/3, NCT05488444). We also address the open issues that include off-target editing, host immune reactions, bacterial counter-resistance, regulatory ambiguity, and scalability of manufacturing. Lastly, we provide priority research directions, such as the combination antimicrobial strategies, AI-assisted CRISPR design, and next-generation delivery engineering, none of which will be resolved before routine clinical application of CRISPR-based antimicrobials is achieved.
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Genome Editing with CRISPR-Cas9: A Budding Biological Contrivance for Colorectal Carcinoma Research and its Perspective in Molecular Medicine.
Genome editing is an addition, deletion, or replacement of a gene to remove or initiating explicit and preferred characters in the genome. Utilizing gene-editing tools like CRISPR-Cas9 technology could be accomplished either by gene-based methodology or protein-based technology that has been under scrutiny for the protracted time wherein physical techniques, viral and non-viral strategies have been utilized together. Transplanting ex vivo CRISPR edited cells empowers screening of single guide RNAs with high-throughput and CRISPR based screening in organoids transplantation to validate cancer cells including colorectal carcinoma in various phases of its development and treatment.CRISPR knockout screens have recognized genes that drive interest in colon cancer to develop hallmarks, especially in some cancer cell lines with single guide RNA, to disclose drug resistance mechanisms. One advantage of this method is to deal with CRISPR knockout genomic screening, which disrupts gene expression, rather than the partial knockdown that is mostly done with RNA interference and CRISPR/Cas technology. This technique is used to treat different forms of cancer because of its proficient editing of the target gene, along with the CRISPR/Cas system. Latest research has shown that the CRISPR/Cas gene-editing technique has theoretically reformed the expression in colorectal carcinoma of long non-coding RNA. For the next decade CRISPR/Cas9 technology will positively fuel the development of more in vivo gene editing clinical trials in colon cancer and will have an enormous impact on molecular medicine.
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ReMOT Control Delivery of CRISPR-Cas9 Ribonucleoprotein Complex to Induce Germline Mutagenesis in the Disease Vector Mosquitoes Culex pipiens pallens (Diptera: Culicidae).
The wide distribution of Culex (Cx.) pipiens complex mosquitoes makes it difficult to prevent the transmission of mosquito-borne diseases in humans. Gene editing using CRISPR/Cas9 is an effective technique with the potential to solve the growing problem of mosquito-borne diseases. This study uses the ReMOT Control technique in Culex pipiens pallens (L.) to produce genetically modified mosquitoes. A microinjection system was established by injecting 60 adult female mosquitoes-14 µl injection mixture was required, and no precipitation occurred with ≤1 µl of endosomal release reagents (chloroquine or saponin). The efficiency of delivery of the P2C-enhanced green fluorescent protein-Cas9 (P2C-EGFP-Cas9) ribonucleoprotein complex into the ovary was 100% when injected at 24 h post-bloodmeal (the peak of vitellogenesis). Using this method for KMO knockout, we found that gene editing in the ovary could also occur when P2C-Cas9 RNP complex was injected into the hemolymph of adult Cx. pipiens pallens by ReMOT Control. In the chloroquine group, of the 2,251 G0 progeny screened, 9 individuals showed with white and mosaic eye phenotypes. In the saponin group, of the 2,462 G0 progeny screened, 8 mutant individuals were observed. Sequencing results showed 13 bp deletions, further confirming the fact that gene editing occurred. In conclusion, the successful application of ReMOT Control in Cx. pipiens pallens not only provides the basic parameters (injection parameters and injection time) for this method but also facilitates the study of mosquito biology and control.
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