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

Chemistry, manufacturing and controls strategies for using novel excipients in lipid nanoparticles DOI
Matthew N. O’Brien, David A. Foley,

Roger H. Pak

и другие.

Nature Nanotechnology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 16, 2025

Язык: Английский

Процитировано

4

In Vivo Endothelial Cell Gene Silencing by siRNA‐LNPs Tuned with Lipoamino Bundle Chemical and Ligand Targeting DOI Creative Commons

Mina Yazdi,

Jana Pöhmerer,

Morteza Hasanzadeh Kafshgari

и другие.

Small, Год журнала: 2024, Номер 20(42)

Опубликована: Июнь 25, 2024

Although small-interfering RNAs (siRNAs) are specific silencers for numerous disease-related genes, their clinical applications still require safe and effective means of delivery into target cells. Highly efficient lipid nanoparticles (LNPs) developed siRNA delivery, showcasing the advantages novel pH-responsive lipoamino xenopeptide (XP) carriers. These sequence-defined XPs assembled by branched lysine linkages between cationizable polar succinoyl tetraethylene pentamine (Stp) units apolar fatty acids (LAFs) at various ratios bundle or U-shape topologies. Formulation siRNA-LNPs using LAF

Язык: Английский

Процитировано

9

Lipo-Xenopeptide Polyplexes for CRISPR/Cas9 based Gene editing at ultra-low dose DOI Creative Commons

Janin Germer,

Anna-Lina Lessl,

Jana Pöhmerer

и другие.

Journal of Controlled Release, Год журнала: 2024, Номер 370, С. 239 - 255

Опубликована: Апрель 27, 2024

Double pH-responsive xenopeptide carriers containing succinoyl tetraethylene pentamine (Stp) and lipo amino fatty acids (LAFs) were evaluated for CRISPR/Cas9 based genome editing. Different carrier topologies, variation of LAF/Stp ratios LAF types as Cas9 mRNA/sgRNA polyplexes screened in three different reporter cell lines using genomic targets (Pcsk9, eGFP, mdx exon 23). One U-shaped bundle (B2)-shaped lipo-xenopeptides exhibiting remarkable efficiencies identified. Genome editing potency top observed at sub-nanomolar EC

Язык: Английский

Процитировано

5

Nanoparticle Targeting Strategies for Lipid and Polymer‐Based Gene Delivery to Immune Cells In Vivo DOI Creative Commons
Manav Jain, Xinjie Yu, Jonathan P. Schneck

и другие.

Small Science, Год журнала: 2024, Номер unknown

Опубликована: Июль 30, 2024

Lipid nanoparticles and polymeric are promising biomaterial platforms for robust intracellular DNA mRNA delivery, highlighted by the widespread use of nanoparticle‐ (NP) based vaccines to help end COVID‐19 pandemic. Recent research has sought adapt this nanotechnology transfect engineer immune cells in vivo. The system is an especially appealing target due its involvement many different diseases, ex vivo‐engineered cell therapies like chimeric antigen receptor (CAR) T therapy have already demonstrated remarkable clinical success certain blood cancers. Although gene delivery can potentially address some cost manufacturing concerns associated with current autologous therapies, transfecting vivo challenging. Not only extrahepatic NP lymphoid organs difficult, but particular resistance transfection. Despite these challenges, modular nature NPs allows researchers examine critical structure–function relationships between a particle's properties ability specifically Herein, several nanomaterial components outlined, including targeting ligands, nucleic acid cargo, chemical properties, physical route administration optimal

Язык: Английский

Процитировано

4

MicroRNAs in the Mitochondria–Telomere Axis: Novel Insights into Cancer Development and Potential Therapeutic Targets DOI Open Access
José Alfonso Cruz-Ramos,

Emmanuel De La Mora-Jiménez,

Beatriz Alejandra Llanes-Cervantes

и другие.

Genes, Год журнала: 2025, Номер 16(3), С. 268 - 268

Опубликована: Фев. 25, 2025

The mitochondria–telomere axis is recognized as an important factor in the processes of metabolism, aging and oncogenesis. MicroRNAs (miRNAs) play essential function this complex interaction, having impact on aspects such cellular homeostasis, oxidative responses apoptosis. In recent years, miRNAs have been found to be crucial for telomeric stability, well mitochondrial behavior, factors that influence cell proliferation viability. Furthermore, (mitomiRs) are associated with gene expression activity cGAS/STING pathway activity, linking DNA recognition immune system responses. Hence, maintain a link biogenesis, metabolic changes cancer organelles. This review focuses roles variety progression their potential application biomarkers or therapeutic agents.

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

2