Current Non-Viral-Based Strategies to Manufacture CAR-T Cells DOI Open Access

Leon Gehrke,

Vasco Dos Reis Gonçalves,

Dominik Andrae

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(24), С. 13685 - 13685

Опубликована: Дек. 21, 2024

The successful application of CAR-T cells in the treatment hematologic malignancies has fundamentally changed cancer therapy. With increasing numbers registered cell clinical trials, efforts are being made to streamline and reduce costs manufacturing while improving their safety. To date, all approved products have relied on viral-based gene delivery genomic integration methods. While viral vectors offer high transfection efficiencies, concerns regarding potential malignant transformation coupled with costly time-consuming vector constant drivers search for cheaper, easier-to-use, safer, more efficient alternatives. In this review, we examine different non-viral transfer methods as alternatives production, advantages disadvantages, examples applications. Transposon-based lead stable but non-targeted integration, easy handle, achieve rates. Programmable endonucleases allow targeted reducing risk integration-mediated cells. Non-integrating CAR-encoding avoid completely only transient CAR expression. these promising alternative techniques transfer, avenues open fully exploiting next-generation therapy applying it a wide range

Язык: Английский

CRISPR-Cas9 Gene Therapy: Non-Viral Delivery and Stimuli-Responsive Nanoformulations DOI Creative Commons
Hyun-Woo Lee, Won‐Yeop Rho,

Yoon-Hee Kim

и другие.

Molecules, Год журнала: 2025, Номер 30(3), С. 542 - 542

Опубликована: Янв. 24, 2025

The CRISPR-Cas9 technology, one of the groundbreaking genome editing methods for addressing genetic disorders, has emerged as a powerful, precise, and efficient tool. However, its clinical translation remains hindered by challenges in delivery efficiency targeting specificity. This review provides comprehensive analysis structural features, advantages, potential applications various non-viral stimuli-responsive systems, examining recent progress to emphasize address these limitations advance therapeutics. We describe how reports that nonviral vectors, including lipid-based nanoparticles, extracellular vesicles, polymeric gold mesoporous silica can offer diverse advantages enhance stability, cellular uptake, biocompatibility, based on their structures physio-chemical stability. also summarize nanoformulations, type vector, introduce precision control delivery. Stimuli-responsive nanoformulations are designed respond pH, redox states, external triggers, facilitate controlled targeted delivery, minimize off-target effects. insights our suggest future gene therapy technologies highlight systems CRISPR-Cas9’s efficacy, positioning them pivotal tools gene-editing therapies.

Язык: Английский

Процитировано

1

Efficient intracellular delivery of CRISPR-Cas9 ribonucleoproteins using dendrimer nanoparticles for robust genomic editing DOI
Wathsala Liyanage,

Gokul Kannan,

Sujatha Kannan

и другие.

Nano Today, Год журнала: 2025, Номер 61, С. 102654 - 102654

Опубликована: Янв. 31, 2025

Язык: Английский

Процитировано

0

Dendritic Cell-Based Glioblastoma Vaccines: Advances and Challenges DOI Creative Commons
Zuowen Zhang, Mingchang Li, Jie Huang

и другие.

IntechOpen eBooks, Год журнала: 2025, Номер unknown

Опубликована: Фев. 14, 2025

Glioblastoma (GBM) is the most aggressive malignancy of central nervous system. Despite advances in standard treatments such as surgery, radiotherapy, and chemotherapy, patients have a very poor prognosis. Tumor vaccines based on dendritic cells (DCs) provide promising new approach for GBM treatment. DCs, effective antigen-presenting cells, initiate adaptive immune responses by activating tumor-specific T cells. However, immunosuppressive microenvironment (characterized regulatory myeloid suppressor factors) physical barrier blood-brain (BBB) greatly limit efficacy DC vaccines. This chapter explores biological basis, preparation process, clinical progress, challenges, future directions DC-based Key aspects antigen selection, vitro culture activation, loading, delivery strategies are analyzed detail. Early trials demonstrated safety potential vaccines, while combination therapies reprogramming being used to overcome existing obstacles. precision personalization highlight their focus immunotherapy research. We believe that with continuous advancement technology interdisciplinary collaboration, can significantly improve survival rate quality life patients.

Язык: Английский

Процитировано

0

Engineered Metal–Organic Frameworks for Targeted CRISPR/Cas9 Gene Editing DOI Creative Commons
Navid Rabiee, Mohammad Rabiee

ACS Pharmacology & Translational Science, Год журнала: 2025, Номер 8(4), С. 1028 - 1049

Опубликована: Март 12, 2025

The development of precise and efficient delivery systems is pivotal for advancing CRISPR/Cas9 gene-editing technologies, particularly therapeutic applications. Engineered metal-organic frameworks (MOFs) have emerged as a promising class inorganic nonviral vectors, offering unique advantages such tunable porosity, high cargo-loading capacity, biocompatibility. This review explores the design application MOF-based nanoplatforms tailored targeted components, aiming to enhance precision efficiency. By incorporating stimuli-responsive linkers bioactive ligands, these MOFs enable controlled release payloads at target site. Comparative discussions demonstrate superior performance over conventional in terms stability, transfection efficiency, reduced off-target effects. Additionally, intracellular trafficking mechanisms potential platforms preclinical models are discussed. These findings highlight transformative overcoming challenges associated with immunogenicity cytotoxicity, paving way their medicine. provides blueprint integration nanotechnology genome editing, frontier systems.

Язык: Английский

Процитировано

0

Evidence-Based Nutraceuticals Derived from Antrodia cinnamomea DOI Creative Commons

Chunyuhang Xu,

Qingtong Xie,

Chien-Liang Kuo

и другие.

Foods, Год журнала: 2025, Номер 14(7), С. 1212 - 1212

Опубликована: Март 30, 2025

Antrodia cinnamomea (A. cinnamomea), a medicinal and edible mushroom endemic to Taiwan, has been traditionally valued as health tonic. Recent studies have highlighted the diverse specialized metabolites bioactive potential of this substance, primarily attributed key secondary such benzenoids, maleic succinic acids, ubiquinone, triterpenoids, primary metabolite polysaccharides. These compounds exhibit broad spectrum pharmacological properties, including those related antibacterial, antitumor, anti-inflammation, hepatoprotection, hypoglycaemia, antioxidant activities, immunomodulation gut microbiota regulation. findings highlight therapeutic A. its applications in supplements functional foods. This review evaluated recent advancements cultivation, extraction, characterization from cinnamomea, with particular focus on submerged solid-state fermentation methods. We hope provide comprehensive framework for promoting efficient scientific evidence based utilization novel strategies health-related innovations.

Язык: Английский

Процитировано

0

Efficient DNA- and virus-free engineering of cellular transcriptomic states using dCas9 ribonucleoprotein (dRNP) complexes DOI Creative Commons
Tara Schmidt,

Maximilian Wiesbeck,

Luisa Egert

и другие.

Nucleic Acids Research, Год журнала: 2025, Номер 53(6)

Опубликована: Март 20, 2025

Abstract For genome editing, the use of CRISPR ribonucleoprotein (RNP) complexes is well established and often superior choice over plasmid-based or viral strategies. RNPs containing dCas9 fusion proteins, which enable targeted manipulation transcriptomes epigenomes, remain significantly less accessible. Here, we describe production, delivery, optimization second generation CRISPRa (dRNPs). We characterize transcriptional cellular consequences dRNP treatments in a variety human target cells show that uptake very efficient. The activation genes demonstrates remarkable potency, even for are strongly silenced, such as developmental master transcription factors. In contrast to DNA-based strategies, gene immediate characterized by sharp temporal precision. also dRNPs allow high-target multiplexing, enabling undiminished multiple simultaneously. Applying these insights, find intensive multiplexing at single promoters synergistically elevates transcription. Finally, demonstrate stem differentiated preferable features instruct convert cell fates efficiently without need DNA delivery vectors.

Язык: Английский

Процитировано

0

Interallelic gene conversion of leukemia-associated single nucleotide variants DOI
Alexander J. Silver, Donovan Brown, Sarah D. Olmstead

и другие.

Gene, Год журнала: 2025, Номер 958, С. 149493 - 149493

Опубликована: Апрель 11, 2025

Язык: Английский

Процитировано

0

Current Non-Viral-Based Strategies to Manufacture CAR-T Cells DOI Open Access

Leon Gehrke,

Vasco Dos Reis Gonçalves,

Dominik Andrae

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(24), С. 13685 - 13685

Опубликована: Дек. 21, 2024

The successful application of CAR-T cells in the treatment hematologic malignancies has fundamentally changed cancer therapy. With increasing numbers registered cell clinical trials, efforts are being made to streamline and reduce costs manufacturing while improving their safety. To date, all approved products have relied on viral-based gene delivery genomic integration methods. While viral vectors offer high transfection efficiencies, concerns regarding potential malignant transformation coupled with costly time-consuming vector constant drivers search for cheaper, easier-to-use, safer, more efficient alternatives. In this review, we examine different non-viral transfer methods as alternatives production, advantages disadvantages, examples applications. Transposon-based lead stable but non-targeted integration, easy handle, achieve rates. Programmable endonucleases allow targeted reducing risk integration-mediated cells. Non-integrating CAR-encoding avoid completely only transient CAR expression. these promising alternative techniques transfer, avenues open fully exploiting next-generation therapy applying it a wide range

Язык: Английский

Процитировано

1