Lipid Nanoparticles With Fine‐Tuned Composition Show Enhanced Colon Targeting as a Platform for mRNA Therapeutics DOI Creative Commons
Riccardo Rampado, Gonna Somu Naidu, Olga Karpov

и другие.

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 25, 2024

Abstract Lipid Nanoparticles (LNPs) recently emerged as an invaluable RNA delivery platform. With many LNP‐based therapeutics in the pre‐clinical and clinical pipelines, there is extensive research dedicated to improving LNPs. These efforts focus mainly on tolerability transfectability of new ionizable lipids RNAs, or modulating LNPs biodistribution with active targeting strategies. However, most formulations follow well‐established lipid proportions used clinically approved products. Nevertheless, investigating effects composition their can expand toolbox for particle design, leading improved Herein, a (30‐n‐LNPs) formulation increasing amounts phospholipids investigated possible mRNA system treating Inflammatory Bowel Diseases. Compared benchmark (b‐LNPs), n‐LNPs containing 30% distearoylphosphatidylcholine (DSPC) are well tolerated following intravenous administration display natural toward inflamed colon dextran sodium sulfate (DSS)‐colitis bearing mice, while de‐targeting clearing organs such liver spleen. Using interleukin‐10‐encoding therapeutic cargo, demonstrated reduction pathological burden colitis‐bearing mice. represent starting point further investigate influence systemic biodistribution, ultimately opening modalities different pathologies.

Язык: Английский

Strategies for non-viral vectors targeting organs beyond the liver DOI
Jeonghwan Kim, Yulia Eygeris, Renee C. Ryals

и другие.

Nature Nanotechnology, Год журнала: 2023, Номер 19(4), С. 428 - 447

Опубликована: Дек. 27, 2023

Язык: Английский

Процитировано

60

Dynamic carriers for therapeutic RNA delivery DOI Creative Commons
Simone Berger, Ulrich Lächelt, Ernst Wagner

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(11)

Опубликована: Март 4, 2024

Carriers for RNA delivery must be dynamic, first stabilizing and protecting therapeutic during to the target tissue across cellular membrane barriers then releasing cargo in bioactive form. The chemical space of carriers ranges from small cationic lipids applied lipoplexes lipid nanoparticles, over medium-sized sequence-defined xenopeptides, macromolecular polycations polyplexes polymer micelles. This perspective highlights discovery distinct virus-inspired dynamic processes that capitalize on mutual nanoparticle–host interactions achieve potent delivery. From host side, subtle alterations pH, ion concentration, redox potential, presence specific proteins, receptors, or enzymes are cues, which recognized by nanocarrier via designs including cleavable bonds, alterable physicochemical properties, supramolecular assembly–disassembly respond changing biological microenvironment

Язык: Английский

Процитировано

23

mRNA therapies: Pioneering a new era in rare genetic disease treatment DOI
Guobo Shen, Jian Liu,

Hanmei Yang

и другие.

Journal of Controlled Release, Год журнала: 2024, Номер 369, С. 696 - 721

Опубликована: Апрель 13, 2024

Язык: Английский

Процитировано

20

Leveraging aptamers for targeted protein degradation DOI Open Access
Zhihao Yang, Qiuxiang Pang, Jun Zhou

и другие.

Trends in Pharmacological Sciences, Год журнала: 2023, Номер 44(11), С. 776 - 785

Опубликована: Июнь 26, 2023

Язык: Английский

Процитировано

25

Circular mRNA Vaccine against SARS-COV-2 Variants Enabled by Degradable Lipid Nanoparticles DOI
Ke Huang, Na Li, Yingwen Li

и другие.

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

The emergence of mRNA vaccines offers great promise and a potent platform in combating various diseases, notably COVID-19. Nevertheless, challenges such as inherent instability potential side effects current delivery systems underscore the critical need for advancement stable, safe, efficacious vaccines. In this study, robust vaccine (cmRNA-1130) eliciting immune activation has been developed from biodegradable lipid with eight ester bonds branched tail (AX4) synthetic circular (cmRNA) encoding trimeric Delta receptor binding domain SARS-CoV-2 spike protein. Notably, cmRNA-1130 exhibits outstanding stability, remaining effective after six months storage at 4 °C multiple freeze–thaw cycles. comparison commercial MC3 lipid, nanoparticles formed degradable AX4 revealed much faster metabolic rate liver spleen, affording negligible impairment to hepatorenal function. Following intramuscular administration, generates sustained neutralizing antibodies induces RBD-specific CD4+ CD8+ T effector memory cells (TEM) Th1-biased mice. Featured activation, high decent safety, cmRNA hold huge clinical prophylaxis treatment different diseases.

Язык: Английский

Процитировано

2

Reprogramming activated hepatic stellate cells by siRNA-loaded nanocarriers reverses liver fibrosis in mice DOI Creative Commons
Mahmoud A. Younis, Yusuke Sato, Yaser Hosny Ali Elewa

и другие.

Journal of Controlled Release, Год журнала: 2023, Номер 361, С. 592 - 603

Опубликована: Авг. 17, 2023

Язык: Английский

Процитировано

20

A new era of targeting cystic fibrosis with non-viral delivery of genomic medicines DOI
Namratha Turuvekere Vittala Murthy,

Kseniia Vlasova,

Jonas Renner

и другие.

Advanced Drug Delivery Reviews, Год журнала: 2024, Номер 209, С. 115305 - 115305

Опубликована: Апрель 16, 2024

Язык: Английский

Процитировано

8

Lipid nanoparticles for nucleic acid delivery beyond the liver DOI

Nadine Saber,

Mariona Estapé Sentí,

Raymond M. Schiffelers

и другие.

Human Gene Therapy, Год журнала: 2024, Номер 35(17-18), С. 617 - 627

Опубликована: Авг. 14, 2024

Lipid nanoparticles (LNPs) are the most clinically advanced drug delivery system for nucleic acid therapeutics, exemplified by success of COVID-19 mRNA vaccines. However, their clinical use is currently limited to hepatic diseases and vaccines due tendency accumulate in liver upon intravenous administration. To fully leverage potential, it essential understand address tropism, while also developing strategies enhance tissues beyond liver. Ensuring that these therapeutics reach target cells avoiding off-target both efficacy safety. There three potential targeting strategies-passive, active, endogenous-which can be used individually or combination nonhepatic tissues. In this review, we delve into recent advancements LNP engineering delivering

Язык: Английский

Процитировано

7

Zwitterionic materials for nucleic acid delivery and therapeutic applications DOI
Shun He, Shuai Liu

Journal of Controlled Release, Год журнала: 2023, Номер 365, С. 919 - 935

Опубликована: Дек. 19, 2023

Язык: Английский

Процитировано

17

Nano–Bio Interactions: Exploring the Biological Behavior and the Fate of Lipid-Based Gene Delivery Systems DOI
Seigo Kimura,

Hideyoshi Harashima

BioDrugs, Год журнала: 2024, Номер 38(2), С. 259 - 273

Опубликована: Фев. 12, 2024

Язык: Английский

Процитировано

5