Small Interfering RNA in Kidney Diseases: Promises and Limitations DOI Creative Commons
Attilio Losito,

Giuseppe Solano

Kidney and Dialysis, Journal Year: 2024, Volume and Issue: 5(1), P. 1 - 1

Published: Dec. 29, 2024

Small interfering RNAs (siRNAs) are short, double-stranded RNA molecules that play a crucial role in the regulation of gene expression, particularly through natural process called interference (RNAi). Their discovery, about 25 years ago, paved way for whole series research leading to synthetic molecules. The silencing potential these siRNAs was initially oriented towards diseases resulting from genetic dysfunctions. This led development first approved human use hereditary transthyretin amyloidosis. Subsequently, field application expanded beyond confines diseases. refinement pharmacological techniques has synthesis variety capable blocking production individual proteins responsible various disease conditions, thus expanding their therapeutic application. kidney also been affected by this new tool, largely indirectly but also, with some difficulty, directly. structural complexity made search targeting its components very challenging. Nevertheless, results technology beginning be seen experimental animals and humans. have treatment amyloidosis patisiran oxalosis lumasiran nedosiran. Studies ongoing as anti-complement drugs IgA nephropathy, angiotensinogen inhibitors hypertension, or against mediators acute injury. In review, biological mechanisms underlying briefly exposed. analyzed discussed.

Language: Английский

Recent Advances in Lipid Nanoparticles and Their Safety Concerns for mRNA Delivery DOI Creative Commons
Jialiang Wang,

Yaopeng Ding,

K. Chul Chong

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(10), P. 1148 - 1148

Published: Oct. 8, 2024

The advent of lipid nanoparticles (LNPs) as a delivery platform for mRNA therapeutics has revolutionized the biomedical field, particularly in treating infectious diseases, cancer, genetic disorders, and metabolic diseases. Recent Advances Therapeutic LNPs: LNPs, composed ionizable lipids, phospholipids, cholesterol, polyethylene glycol (PEG) facilitate efficient cellular uptake cytosolic release while mitigating degradation by nucleases. However, synthetic entities, LNPs face challenges that alter their therapeutic efficacy safety concerns. Toxicity/Reactogenicity/Immunogenicity: This review provides comprehensive overview latest advancements LNP research, focusing on preclinical assessments encompassing toxicity, reactogenicity, immunogenicity. Summary Outlook: Additionally, it outlines potential strategies addressing these offers insights into future research directions enhancing application therapeutics.

Language: Английский

Citations

16
Nucleic acid delivery by lipid nanoparticles for organ targeting DOI
Jialin Guo,

Mingrui Gu,

Y Chen

et al.

Chinese Chemical Letters, Journal Year: 2025, Volume and Issue: unknown, P. 110849 - 110849

Published: Jan. 1, 2025

Language: Английский

Citations

1
Navigating the intricate in-vivo journey of lipid nanoparticles tailored for the targeted delivery of RNA therapeutics: a quality-by-design approach DOI Creative Commons

Ehsan Bitaraf Haghighi,

Samira Sadat Abolmaali, Ali Dehshahri

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Nov. 14, 2024

RNA therapeutics, such as mRNA, siRNA, and CRISPR–Cas9, present exciting avenues for treating diverse diseases. However, their potential is commonly hindered by vulnerability to degradation poor cellular uptake, requiring effective delivery systems. Lipid nanoparticles (LNPs) have emerged a leading choice in vivo delivery, offering protection against degradation, enhanced facilitation of endosomal escape. LNPs encounter numerous challenges targeted vivo, demanding advanced particle engineering, surface functionalization with targeting ligands, profound comprehension the biological milieu which they function. This review explores structural physicochemical characteristics LNPs, in-vivo fate, customization therapeutics. We highlight quality-by-design (QbD) approach beyond liver, focusing on biodistribution, immunogenicity, toxicity. In addition, we explored current strategies associated ensuring repeated-dose efficacy, safety, tissue-specific gene delivery. Furthermore, provide insights into clinical applications various classes diseases finally prospects

Language: Английский

Citations

8
Development and Validation of AAV-Mediated Liver, Liver-VAT, and Liver-Brain SORT and Therapeutic Regulation of FASN in Hepatic De Novo Lipogenesis DOI Creative Commons
Ratulananda Bhadury,

Mohammad Athar,

Pooja Mishra

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(5), P. 372 - 372

Published: March 4, 2025

Hepatic lipogenesis combined with elevated endoplasmic reticulum (ER) stress is central to non-alcoholic steatohepatitis (NASH). However, the therapeutic targeting of key molecules considerably less accomplished. Adeno-associated virus (AAV)-mediated gene therapies offer a new solution for various human ailments. Comprehensive bio-functional validation studies are essential assess impact AAVs in target organ developing both preclinical and clinical therapy programs. Here, we have established robust efficient protocol high-titer AAV production enable detailed Selective ORgan Targeting (SORT) AAV1, 5, 7, 8 vivo. Our results vivo SORT showed single (liver) by AAV8, no dual transduction (liver-brain liver-VAT) AAV5 AAV7. Using dataset murine models NASH, identified an inverse correlation between ER stress-triggered CRELD2 de novo driver FASN. Furthermore, liver-specific silencing via AAV8-shCreld2 strongly supports contribution through FASN regulation. Thus, our study demonstrates method producing clinically translatable that could be readily adapted liver and/or liver-VAT or liver-brain targeted therapy.

Language: Английский

Citations

0
Hydrophobically modified poly(glycidyl amine)s enables effective siRNA delivery and target gene silencing in lungs DOI
Qi Shuai, Siyuan Chen,

Wanxuan Xie

et al.

Journal of Drug Delivery Science and Technology, Journal Year: 2025, Volume and Issue: unknown, P. 106995 - 106995

Published: May 1, 2025

Language: Английский

Citations

0
Application of siRNA technology in cytochrome P450 gene modulation DOI

Wenzhao Jiang,

Rosemary Sang,

Cai Zhang

et al.

Drug Metabolism and Disposition, Journal Year: 2025, Volume and Issue: 53(3), P. 100040 - 100040

Published: Jan. 21, 2025

Cytochrome P450 plays key roles in the biotransformation of endogenous and exogenous chemicals including drugs environmental pollutants. The inhibition downregulation P450s can have therapeutic effects, and/or modulate drug metabolism. are largely inhibited by small molecules; however, this strategy is often hampered intrinsic toxicity drug-drug interactions. Furthermore, it challenging for molecules to exhibit high selectivity inhibitory efficiencies. Recently, interfering RNA (siRNA) technology has demonstrated potential modulation. Examples recent applications siRNAs gene modulation, vitro vivo, highlighted review. necessity siRNA techniques their advantages as modulators discussed, along with a review current obstacles perspective on future advancements. SIGNIFICANCE STATEMENT: This article reviews studies application cytochrome methods benefits use been suggested comparison small-molecule drugs. Additionally, challenges that presently limit broader implementation topic examined, developments proposed.

Language: Английский

Citations

0
A Quarter Century of Calcium-Permeable Ion Channel, TRPV4: Perspectives on Expression and Function in Endothelial Cells - Time to Translate DOI
Wolfgang Liedtke

Published: Jan. 1, 2025

Language: Английский

Citations

0
Screening Natural Cholesterol Analogs to Assemble Self‐Adjuvant Lipid Nanoparticles for Antigens Tagging Guided Therapeutic Tumor Vaccine DOI
Shuang Liang, Shuying Gao,

Shunli Fu

et al.

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: April 26, 2025

Abstract The clinical progress of tumor nucleotide vaccines is limited due to insufficient recognition and killing cells with low antigen expression by cytotoxic T lymphocytes (CTL). Here, natural cholesterol analogs are screened assemble self‐adjuvant lipid nanoparticles (LNPs) for antigens tagging dendritic (DC) activation. First, a library ginsenosides collected, then according their anti‐tumor immunity. Then, ginsenoside‐Rg3 based‐LNPs loaded (Rg3‐LNPs) identified as the optimal formulation investigating physicochemical biological properties. Finally, Rg3‐LNPs granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) co‐loaded into macroporous hydrogel long‐term immune response. could accumulate both tumors LNs. targeted high glucose transporter‐1 via targeting ligand Rg3, anchored on cell surface, thus promoting CTL cells; can LNs promote DC activation presentation, stimulating Besides, an adjuvant, cooperated GM‐CSF remodel microenvironment, cells. Collectively, this work highlights importance in vaccine has great value immune‐escaping tumors.

Language: Английский

Citations

0
Tannylated lipid nanoparticles for prolonged circulation and PET imaging-guided cancer therapy DOI
Yeli Fan,

Wujun Miao,

Rong Yan

et al.

Biomaterials Advances, Journal Year: 2025, Volume and Issue: 175, P. 214325 - 214325

Published: May 1, 2025

Language: Английский

Citations

0
Cell Membrane‐Coated Lipid Nanoparticles for Drug Delivery DOI Creative Commons
Moataz B. Zewail, Guangze Yang,

Yilong Fan

et al.

Aggregate, Journal Year: 2025, Volume and Issue: unknown

Published: May 5, 2025

ABSTRACT Cell membrane coating (CMC) of nanoparticles (NPs) has emerged as a prominent strategy that gained significant attention and achieved notable progress across various therapeutic sectors. Coating NPs with natural cell membranes endows them functions addresses challenges in drug delivery, such prolonging circulation time, reducing immunogenicity, improving targeting efficiency cellular communication. Among the different NPs, lipid (LNPs) have revolutionized field nanomedicine by providing advantageous features for delivery. The versatile characteristics LNPs synergize well membranes’ biomimetic properties, creating hybrid structures enhanced functionalities diverse biomedical applications. A more advanced form significantly capabilities can be through CMC. However, opportunities remain further advancements, ongoing efforts focused on discovering innovative applications fully harnessing potential this promising combination. This article provides critical review recent coated‐LNPs (CMC‐LNPs). First, LNP types, their preparation methods, strategies are summarized. development, functions, CMC‐LNPs then discussed. Last, advantages, limitations, challenges, future perspectives presented.

Language: Английский

Citations

0