Prime editing: advances and therapeutic applications

Trends in biotechnology, Год журнала: 2023, Номер 41(8), С. 1000 - 1012

Опубликована: Март 30, 2023

Clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR–Cas)-mediated genome editing has revolutionized biomedical research and will likely change the therapeutic diagnostic landscape. However, CRISPR–Cas9, which edits DNA by activating double-strand break (DSB) repair pathways, is not always sufficient for gene therapy applications where precise mutation required. Prime editing, latest revolution in genome-editing technologies, can achieve any possible base substitution, insertion, or deletion without requirement DSBs. prime still its infancy, further development needed to improve efficiency delivery strategies applications. We summarize developments optimization of editor (PE) variants with improved precision. Moreover, we highlight some potential

Язык: Английский

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Targeting miRNA by CRISPR/Cas in cancer: advantages and challenges

Military Medical Research, Год журнала: 2023, Номер 10(1)

Опубликована: Июль 17, 2023

Clustered regulatory interspaced short palindromic repeats (CRISPR) has changed biomedical research and provided entirely new models to analyze every aspect of sciences during the last decade. In study cancer, CRISPR/CRISPR-associated protein (Cas) system opens avenues into issues that were once unknown in our knowledge noncoding genome, tumor heterogeneity, precision medicines. CRISPR/Cas-based gene-editing technology now allows for precise permanent targeting mutations provides an opportunity target small non-coding RNAs such as microRNAs (miRNAs). However, development effective safe cancer gene editing therapy is highly dependent on proper design be innocuous normal cells prevent introducing other abnormalities. This aims highlight cutting-edge approaches cancer-gene based CRISPR/Cas miRNAs therapy. Furthermore, we potential challenges CRISPR/Cas-mediated miRNA offer advanced strategies overcome them.

Язык: Английский

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Mitochondrial dysfunction and skeletal muscle atrophy: Causes, mechanisms, and treatment strategies

Mitochondrion, Год журнала: 2023, Номер 72, С. 33 - 58

Опубликована: Июль 13, 2023

Язык: Английский

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Recent advances in the delivery and applications of nonviral CRISPR/Cas9 gene editing

Drug Delivery and Translational Research, Год журнала: 2023, Номер 13(5), С. 1500 - 1519

Опубликована: Март 29, 2023

Язык: Английский

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Immunogenicity of CRISPR therapeutics—Critical considerations for clinical translation

Frontiers in Bioengineering and Biotechnology, Год журнала: 2023, Номер 11

Опубликована: Фев. 16, 2023

CRISPR offers new hope for many patients and promises to transform the way we think of future therapies. Ensuring safety therapeutics is a top priority clinical translation specific recommendations have been recently released by FDA. Rapid progress in preclinical development leverages years experience with gene therapy successes failures. Adverse events due immunogenicity major setback that has impacted field therapy. As several vivo trials make progress, challenge remains significant roadblock availability utility therapeutics. In this review, examine what currently known about discuss considerations mitigate design safe clinically translatable

Язык: Английский

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Principles of CRISPR-Cas9 technology: Advancements in genome editing and emerging trends in drug delivery

Journal of Drug Delivery Science and Technology, Год журнала: 2024, Номер 92, С. 105338 - 105338

Опубликована: Янв. 6, 2024

The rapid advancement of CRISPR-Cas9 technology has instigated a profound transformation in genome editing with significant implications for fields like health, agriculture, and biotechnology. This abstract provides an overview the historical significance fundamental components CRISPR-Cas9, notably Cas9 protein guide RNA, underscoring its pivotal role genetic manipulation. It emphasizes CRISPR-Cas9's preeminence domain precise editing, driving breakthroughs personalized medicine, gene therapy, agriculture. Of paramount importance is integration nanomaterials, encompassing lipid-based polymeric nanoparticles, alongside viral vectors, serving as potent vehicles augmenting delivery efficiency precision. We explore strategies aimed at enhancing through while also addressing ethical regulatory considerations. In expert opinion section, we offer nuanced perspective on present state field, highlighting potential transformative progress research therapy. stands brink unlocking new possibilities providing innovative solutions to address pressing global challenges.

Язык: Английский

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Viral and Non-Viral Systems to Deliver Gene Therapeutics to Clinical Targets

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(13), С. 7333 - 7333

Опубликована: Июль 4, 2024

Clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology has revolutionized the field of gene therapy as it enabled precise genome editing with unprecedented accuracy and efficiency, paving way for clinical applications to treat otherwise incurable genetic disorders. Typically, requires delivery multiple components target cells that, depending on platform used, may include messenger RNA (mRNA), complexes, DNA fragments. For purposes, these have be efficiently delivered into transplantable cells, such primary T lymphocytes or hematopoietic stem progenitor that are typically sensitive exogenous substances. This challenge limited broad applicability those strategies which efficient methods available. Electroporation-based methodologies been generally applied applications, but procedure-associated toxicity represented a major burden. With advent novel less disruptive deliver cargo is now possible safely editing, thus expanding strategies. In this review, we describe different systems available components, including viral non-viral systems, highlighting their advantages, limitations, recent applications. Recent improvements achieve cell specificity represent critical development enable in vivo targeting future will certainly play pivotal role field.

Язык: Английский

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CRISPR/Cas9-Mediated Gene Therapy for Glioblastoma: A Scoping Review

Biomedicines, Год журнала: 2024, Номер 12(1), С. 238 - 238

Опубликована: Янв. 21, 2024

This scoping review examines the use of CRISPR/Cas9 gene editing in glioblastoma (GBM), a predominant and aggressive brain tumor. Categorizing targets into distinct groups, this explores their roles cell cycle regulation, microenvironmental dynamics, interphase processes, therapy resistance reduction. The complexity CRISPR-Cas9 applications GBM research is highlighted, providing unique insights apoptosis, proliferation, immune responses within tumor microenvironment. studies challenge conventional perspectives on specific genes, emphasizing potential therapeutic implications manipulating key molecular players dynamics. Exploring GBMs yields significant regulation cellular spanning interphase, renewal, migration. Researchers, by precisely targeting uncover orchestration governing growth, differentiation during critical phases cycle. findings underscore technology unraveling complex dynamics microenvironment, offering promising avenues for targeted therapies to curb growth. also outlines addressing GBM, employing target genes associated with chemotherapy resistance, showcasing its transformative effective treatments.

Язык: Английский

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Comparative analysis of lipid Nanoparticle-Mediated delivery of CRISPR-Cas9 RNP versus mRNA/sgRNA for gene editing in vitro and in vivo

European Journal of Pharmaceutics and Biopharmaceutics, Год журнала: 2024, Номер 196, С. 114207 - 114207

Опубликована: Фев. 6, 2024

The discovery that the bacterial defense mechanism, CRISPR-Cas9, can be reprogrammed as a gene editing tool has revolutionized field of editing. CRISPR-Cas9 introduce double-strand break at specific targeted site within genome. Subsequent intracellular repair mechanisms double strand either lead to knock-out (via non-homologous end-joining pathway) or correction in presence DNA template via homology-directed repair. With latter, pathological mutations cut out and repaired. Advances are being made utilize patients by incorporating its components into non-viral delivery vehicles will protect them from premature degradation deliver tissues. Herein, delivered form three different cargos: plasmid DNA, RNA ribonucleoprotein complex (RNP). We others have recently shown Cas9 RNP efficiently formulated lipid-nanoparticles (LNP) leading functional vitro. In this study, we compared LNP encapsulating mRNA Cas9, sgRNA HDR against containing Cas9-RNP template. Former showed smaller particle sizes, better protection degrading enzymes higher efficiencies on both reporter HEK293T cells HEPA 1–6 vitro assays. Both formulations were additionally tested female Ai9 mice biodistribution efficiency after systemic administration. delivering retained mainly liver, with Cas9-RNPs found spleen lungs. Finally, could only concluded for sgRNA. These LNPs resulted 60 % hepatocytes. Delivery cargo format was thereby surpass application vivo.

Язык: Английский

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Combination therapy based on dual-target biomimetic nano-delivery system for overcoming cisplatin resistance in hepatocellular carcinoma

Journal of Nanobiotechnology, Год журнала: 2023, Номер 21(1)

Опубликована: Март 14, 2023

Strategies to overcome toxicity and drug resistance caused by chemotherapeutic drugs for targeted therapy against hepatocellular carcinoma (HCC) are urgently needed. Previous studies revealed that high oxidored-nitro domain-containing protein 1(NOR1) expression in HCC was associated with cisplatin (DDP) resistance. Herein, a novel dual-targeting nanocarrier system AR-NADR generated the treatment of DDP HCC. The core is metal-organic frameworks (MOF) modified nuclear location sequence (NLS), which loading NOR1 shRNA (R). shell an A54 peptide inserted into erythrocyte membrane (AR). Our results show efficiently internalized tumor cells due its specific binding receptors abundantly expressed on surface NLS peptide-mediated entry. Additionally, more likely be released degradation Ag-MOF acidic microenvironment. Moreover, acting as vector gene delivery, effectively inhibits suppressing NOR1, induces intracellular accumulation makes sensitive DDP. Finally, anti-HCC efficacy mechanisms were systematically elucidated HepG2/DDP cell model well model. Therefore, constitutes key strategy achieve excellent silencing antitumor efficacy, provides effective precise strategies

Язык: Английский

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