Environmental Research, Journal Year: 2023, Volume and Issue: 233, P. 116506 - 116506
Published: June 25, 2023
Language: Английский
Nature Reviews Methods Primers, Journal Year: 2022, Volume and Issue: 2(1)
Published: April 14, 2022
Language: Английский
Citations
382
Chinese Chemical Letters, Journal Year: 2022, Volume and Issue: 34(2), P. 107518 - 107518
Published: May 14, 2022
Language: Английский
Citations
343
Bioengineering & Translational Medicine, Journal Year: 2021, Volume and Issue: 6(2)
Published: Feb. 3, 2021
Abstract Ionizable lipid nanoparticles (LNPs) are the most clinically advanced nano‐delivery system for therapeutic nucleic acids. The great effort put in development of ionizable lipids with increased vivo potency brought LNPs from laboratory benches to FDA approval patisiran 2018 and ongoing clinical trials mRNA‐based vaccines against SARS‐CoV‐2. Despite these success stories, several challenges remain RNA delivery, including what is known as “endosomal escape.” Reaching cytosol mandatory unleashing activity molecules, their accumulation other intracellular compartments would simply result efficacy loss. In LNPs, ability form destabilizing non‐bilayer structures at acidic pH recognized key endosomal escape cytosolic delivery. This motivating a surge studies aiming designing novel improved biodegradation safety profiles. this work, we describe journey RNA‐loaded across multiple barriers, extracellular space cytosol. silico molecular dynamics modeling, vitro high‐resolution microscopy analyses, imaging data systematically reviewed distill out regulating mechanisms underlying RNA. Finally, comparison strategies employed by enveloped viruses deliver genetic material into cells also presented. combination multidisciplinary analytical toolkit quantification nature‐inspired design could foster future delivery
Language: Английский
Citations
237
Acta Pharmaceutica Sinica B, Journal Year: 2021, Volume and Issue: 12(2), P. 600 - 620
Published: Aug. 12, 2021
The use of small interfering RNAs (siRNAs) has been under investigation for the treatment several unmet medical needs, including acute lung injury/acute respiratory distress syndrome (ALI/ARDS) wherein siRNA may be implemented to modify expression pro-inflammatory cytokines and chemokines at mRNA level. properties such as clear anatomy, accessibility, relatively low enzyme activity make a good target local therapy. However, translation is restricted by inefficient delivery therapeutics cells due naked siRNA. Thus, this review will focus on various systems that can used different barriers need surmounted development stable inhalable formulations human before ALI/ARDS become available in clinic.
Language: Английский
Citations
178
Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(709)
Published: Aug. 16, 2023
An inhalable platform for messenger RNA (mRNA) therapeutics would enable minimally invasive and lung-targeted delivery a host of pulmonary diseases. Development mRNA has been limited by poor transfection efficiency risk vehicle-induced pathology. Here, we report an polymer-based vehicle therapeutic mRNAs to the lung. We optimized biodegradable poly(amine- co -ester) (PACE) polyplexes using end-group modifications polyethylene glycol. These achieved high throughout lung, particularly in epithelial antigen-presenting cells. applied this technology develop mucosal vaccine severe acute respiratory syndrome coronavirus 2 found that intranasal vaccination with spike protein–encoding induced potent cellular humoral adaptive immunity protected susceptible mice from lethal viral challenge. Together, these results demonstrate translational potential PACE lungs.
Language: Английский
Citations
81
Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 65(10), P. 6975 - 7015
Published: May 9, 2022
In the past decade, there has been a shift in research, clinical development, and commercial activity to exploit many physiological roles of RNA for use medicine. With rapid success development lipid–RNA nanoparticles mRNA vaccines against COVID-19 with several approved RNA-based drugs, catapulted forefront drug research. diverse functions beyond role producing antigens or therapeutic proteins, classes serve regulatory cells tissues. These RNAs have potential as new therapeutics, itself serving either target. Here, based on CAS Content Collection, we provide landscape view current state outline trends research medicine across time, geography, pipelines, chemical modifications, delivery mechanisms.
Language: Английский
Citations
74
Advanced Materials, Journal Year: 2023, Volume and Issue: 36(4)
Published: Aug. 7, 2023
Abstract Lipid nanoparticles (LNPs) are currently the most promising clinical nucleic acids drug delivery vehicles. LNPs prevent degradation of cargo during blood circulation. Upon entry into cell, specific components lipid can promote endosomal escape acids. These basic properties as acid carriers. As exhibit hepatic aggregation characteristics, enhancing targeting out liver is a crucial way to improve administrated in vivo. Meanwhile, loaded often considered inadequate, and therefore, much effort devoted intracellular release efficiency Here, different strategies efficiently deliver from concluded their mechanisms investigated. In addition, based on information that trials or have completed trials, issues necessary be approached translation discussed, which it hoped will shed light development LNP drugs.
Language: Английский
Citations
56
Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 205, P. 115175 - 115175
Published: Jan. 11, 2024
Language: Английский
Citations
41
Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 206, P. 115190 - 115190
Published: Feb. 1, 2024
mRNA-based vaccines are emerging as a promising alternative to standard cancer treatments and the conventional vaccines. Moreover, FDA-approval of three nucleic acid based therapeutics (Onpattro, BNT162b2 mRNA-1273) has further increased interest trust on this type therapeutics. In order achieve significant therapeutic efficacy, mRNA needs from drug delivery system. last years, several platforms have been explored, being lipid nanoparticles (LNPs) most well characterized studied. A better understanding how operate (both itself system) will help improve their efficacy safety. review, we provide an overview what mode action highlight advantages challenges different that under investigation.
Language: Английский
Citations
22
ACS Nano, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 21, 2025
Nucleic acid therapeutics represent a highly promising treatment approach in modern medicine, treating diseases at the genetic level. However, these face numerous challenges practical applications, particularly regarding their stability, effectiveness, cellular uptake efficiency, and limitations delivering them specifically to target tissues. To overcome obstacles, researchers have developed various innovative delivery systems, including viral vectors, lipid nanoparticles, polymer inorganic protein carriers, exosomes, antibody oligonucleotide conjugates, DNA nanostructure-based systems. These systems enhance therapeutic efficacy of nucleic drugs by improving targeting specificity, half-life vivo. In this review, we systematically discuss different types drugs, analyze major barriers encountered delivery, summarize current research progress emerging We also highlight latest advancements application for diseases, infectious cancer, brain wound healing. This review aims provide comprehensive overview drug systems' status future directions integrating nanotechnology, biomaterials science, gene editing technologies, emphasizing transformative potential precision medicine.
Language: Английский
Citations
2