Cited by Gene therapy for β-thalassemia: current and future options

EGFR-targeted ionizable lipid nanoparticles enhance in vivo mRNA delivery to the placenta DOI

Hannah C. Geisler,

Aditi A Ghalsasi,

Hannah C Safford

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 371, P. 455 - 469

Published: June 10, 2024

Language: Английский

Citations

Advanced Delivery Systems for Gene Editing: A Comprehensive Review from the GenE-HumDi COST Action Working group DOI

Alessia Cavazza, Francisco J Molina-Estévez, Álvaro Plaza Reyes

et al.

Molecular Therapy — Nucleic Acids, Journal Year: 2025, Volume and Issue: 36(1), P. 102457 - 102457

Published: Jan. 18, 2025

Language: Английский

Citations

Nature-inspired platform nanotechnology for RNA delivery to myeloid cells and their bone marrow progenitors DOI

Stijn R. J. Hofstraat, Tom Anbergen, Robby Zwolsman

et al.

Nature Nanotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Language: Английский

Citations

Targeted Delivery of mRNA with Polymer–Lipid Nanoparticles for In Vivo Base Editing DOI

Qimingxing Chen,

Yan Chang,

Xiaoyan He

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Messenger RNA (mRNA) encoding base editors, along with single guide RNAs (sgRNAs), have emerged as a promising therapeutic approach for various disorders. However, there is still insufficient exploration in achieving targeted and efficient delivery of mRNA sgRNA to multiple organs while ensuring high biocompatibility stability vivo. To address this challenge, we synthesized library 108 poly(β-amino) esters (PBAEs) by incorporating 100% hydrophobic side chains end-caps varying amines. These PBAEs were further formulated other excipients, including helper lipids, cholesterol, PEGylated form polymer–lipid nanoparticles (PLNPs). Structure–function analysis revealed that eLog P could serve predictive parameter determining the liver or lung tropism PLNPs. The end-capped monoamines was significantly higher compared those diamines. Leveraging these findings, expanded PBAE identified leading (7C8C8) efficiency outperforming current FDA-approved ionizable lipids (ALC-0315, SM-102, Dlin-MC3-DMA). LD50 empty PLNPs determined be 403.8 ± 49.46 mg/kg, indicating safety profile. Additionally, demonstrated sustained transfection activity at least 2 months when stored −20 °C after freezing 4 following lyophilization. Subsequently, vivo editing using achieved an impressive approximately 70% significant reduction protein levels exceeding 90%. Notably, synergistic effects observed through simultaneous disruption proprotein convertase subtilisin/kexin type 9 angiopoietin-like 3 genes, resulting low-density lipoprotein cholesterol over 60% several months. compelling findings provide strong support development platforms mRNA-based therapies.

Language: Английский

Citations

Nano-bio interactions in mRNA nanomedicine: Challenges and opportunities for targeted mRNA delivery DOI

Qimanguli Saiding, Zhongyang Zhang, Shuying Chen

et al.

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 203, P. 115116 - 115116

Published: Oct. 21, 2023

Language: Английский

Citations

Nucleic acid-based drugs for patients with solid tumours DOI

Sebastian G. Huayamares, David Loughrey, Hyejin Kim

et al.

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: 21(6), P. 407 - 427

Published: April 8, 2024

Language: Английский

Citations

The clinical impact of mRNA therapeutics in the treatment of cancers, infections, genetic disorders, and autoimmune diseases DOI

Roham Deyhimfar,

Mehrnaz Izady,

Mohammadreza Shoghi

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(5), P. e26971 - e26971

Published: Feb. 29, 2024

mRNA-based therapeutics have revolutionized medicine and the pharmaceutical industry. The recent progress in optimization formulation of mRNAs has led to development a new therapeutic platform with broad range applications. With growing body evidence supporting use drugs for precision personalized treatments, including cancer immunotherapy, genetic disorders, autoimmune diseases, this emerging technology offers rapidly expanding category options. Furthermore, deployment mRNA vaccines facilitated prompt flexible response medical emergencies, exemplified by COVID-19 outbreak. establishment stable safe molecules carried efficient delivery systems is now available through advances molecular biology nanotechnology. This review aims elucidate advancements clinical applications addressing significant health-related challenges such as cancer, infections provide insights into efficacy safety trials.

Language: Английский

Citations

Unlocking the Therapeutic Applicability of LNP-mRNA: Chemistry, Formulation, and Clinical Strategies DOI

Xiaonan Huang,

Yishan Ma,

Guanghui Ma

et al.

Research, Journal Year: 2024, Volume and Issue: 7

Published: Jan. 1, 2024

Messenger RNA (mRNA) has emerged as an innovative therapeutic modality, offering promising avenues for the prevention and treatment of a variety diseases. The tremendous success mRNA vaccines in effectively combatting coronavirus disease 2019 (COVID-19) evidences unlimited medical potential technology. Overcoming challenges related to stability, immunogenicity, precision targeting been made possible by recent advancements lipid nanoparticles (LNPs). This review summarizes state-of-the-art LNP-mRNA-based therapeutics, including their structure, material compositions, design guidelines, screening principles. Additionally, we highlight current preclinical clinical trends LNP-mRNA therapeutics broad range treatments ophthalmological conditions, cancer immunotherapy, gene editing, rare-disease medicine. Particular attention is given translation evolution into broader spectrum therapeutics. We explore concerns aspects inadequate extrahepatic efficacy, elevated doses, safety concerns, large-scale production procedures. discussion may offer insights perspectives on near- long-term development prospects

Language: Английский

Citations

Designing drug delivery systems for cell therapy DOI

Liwen Wang, Yongsheng Gao, Zhaoqianqi Feng

et al.

Nature Reviews Bioengineering, Journal Year: 2024, Volume and Issue: 2(11), P. 944 - 959

Published: July 15, 2024

Language: Английский

Citations

In utero delivery of targeted ionizable lipid nanoparticles facilitates in vivo gene editing of hematopoietic stem cells DOI

Rohan Palanki, John S. Riley, Sourav K. Bose

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(32)

Published: July 30, 2024

Monogenic blood diseases are among the most common genetic disorders worldwide. These result in significant pediatric and adult morbidity, some can death prior to birth. Novel ex vivo hematopoietic stem cell (HSC) gene editing therapies hold tremendous promise alter therapeutic landscape but not without potential limitations. In offer a potentially safer more accessible treatment for these hindered by lack of delivery vectors targeting HSCs, which reside difficult-to-access bone marrow niche. Here, we propose that this biological barrier be overcome taking advantage HSC residence easily liver during fetal development. To facilitate cargo developed an ionizable lipid nanoparticle (LNP) platform CD45 receptor on surface HSCs. After validating targeted LNPs improved messenger ribonucleic acid (mRNA) lineage cells via CD45-specific mechanism vitro, demonstrated mediated safe, potent, long-term modulation HSCs multiple mouse models. We further optimized LNP vitro encapsulate deliver CRISPR-based nucleic cargos. Finally, showed enhanced at proof-of-concept locus after single utero intravenous injection. By development, our Systematically Targeted Editing Machinery (STEM) may provide translatable strategy treat monogenic before

Language: Английский

Citations