Small and long non-coding RNAs: Past, present, and future

Cell, Journal Year: 2024, Volume and Issue: 187(23), P. 6451 - 6485

Published: Nov. 1, 2024

Language: Английский

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Targeted delivery systems of siRNA based on ionizable lipid nanoparticles and cationic polymer vectors

Biotechnology Advances, Journal Year: 2025, Volume and Issue: 81, P. 108546 - 108546

Published: Feb. 26, 2025

Language: Английский

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Evolving understanding of autoimmune mechanisms and new therapeutic strategies of autoimmune disorders

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 4, 2024

Autoimmune disorders are characterized by aberrant T cell and B reactivity to the body's own components, resulting in tissue destruction organ dysfunction. diseases affect a wide range of people many parts world have become one major concerns public health. In recent years, there been substantial progress our understanding epidemiology, risk factors, pathogenesis mechanisms autoimmune diseases. Current approved therapeutic interventions for mainly non-specific immunomodulators may cause broad immunosuppression that leads serious adverse effects. To overcome limitations immunosuppressive drugs treating diseases, precise target-specific strategies urgently needed. date, significant advances made immune tolerance, offering new avenue developing antigen-specific immunotherapies These approaches shown great potential various preclinical animal models recently evaluated clinical trials. This review describes common manifestation with focus on typical including multiple sclerosis, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, sjögren's syndrome. We discuss current therapeutics developed this field, highlight use nanomaterials mRNA vaccine techniques induce tolerance.

Language: Английский

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Survival strategies of cancer cells: the role of macropinocytosis in nutrient acquisition, metabolic reprogramming, and therapeutic targeting

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

Published: Jan. 16, 2025

Macropinocytosis is a nonselective form of endocytosis that allows cancer cells to largely take up the extracellular fluid and its contents, including nutrients, growth factors, etc. We first elaborate meticulously on process macropinocytosis. Only by thoroughly understanding this entire can we devise targeted strategies against it. then focus central role MTOR (mechanistic target rapamycin kinase) complex 1 (MTORC1) in regulating macropinocytosis, highlighting significance as key signaling hub where various pathways converge control nutrient uptake metabolic processes. The article covers comprehensive analysis literature molecular mechanisms governing initiation, maturation, recycling macropinosomes, with an emphasis how these processes are hijacked sustain their growth. Key discussions include potential therapeutic targeting such enhancing drug delivery via pathway, inhibiting macropinocytosis starve cells, blocking degradation inducing methuosis – cell death triggered excessive Targeting represents novel innovative approach could significantly advance treatment cancers rely pathway for survival. Through continuous research innovation, look forward developing more effective safer anti-cancer therapies will bring new hope patients.

Language: Английский

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An update on nanocarriers for follicular-targeted drug delivery for androgenetic alopecia topical treatment

Expert Opinion on Drug Delivery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Introduction Androgenic alopecia is a multifactorial disease with high incidence and great psychological burden on patients. The current FDA-approved treatment topical minoxidil or oral finasteride. However, both present significant limitations. While the systemic absorption of finasteride causes serious sexual side effects, minoxidil's low solubility imposes challenge in obtaining non-irritative effective formulation. One way to solve such limitations by using nanocarriers targeting drug delivery hair follicles upon application.

Language: Английский

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RNA-based therapies in liver metabolic diseases

Gut, Journal Year: 2025, Volume and Issue: unknown, P. gutjnl - 331742

Published: Feb. 23, 2025

RNA-based therapeutics have rapidly emerged over the past decade, offering a new class of medicines that differ significantly from conventional drugs. These therapies can be programmed to target or restore defective genes, allowing for more personalised treatments and reducing side effects. Notably, RNA made significant progress in treatment genetic liver diseases, exemplified by small interfering hereditary transthyretin amyloidosis, which use liver-targeting strategies such as GalNAc conjugation improve efficacy safety. gene-editing technologies, base editor prime clustered regularly interspaced short palindromic repeats systems, also show promise with their ability minimise genomic rearrangements cancer risk. While offer high precision, challenges remain optimising delivery methods ensuring long-term safety efficacy. Lipid nanoparticle-mRNA therapeutics, particularly protein replacement rare gained support preclinical successes. Compared viral gene therapies, mRNA present safer profile reduced risks integration oncogene activation. However, clinical trials, especially face limitations sample sizes observation periods. Further studies, including non-human primates, will essential refining trial designs. Despite potential, costs pose challenge require cost–utility models guide pricing accessibility. Here, we discuss fundamental aspects showcase most relevant developments metabolic diseases.

Language: Английский

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GalNAc End‐Capped Poly(β‐amino ester)s with Screened Side Chains for Efficient Gene Delivery

Small Methods, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Abstract Plasmids are widely used gene vectors in therapy, yet their efficient delivery remains a major challenge for achieving optimal therapeutic outcomes. Recently, poly(β‐amino esters) (PBAEs) have emerged as promising carriers non‐viral due to tunable structures and high efficiency. Nonetheless, the cationic nature of PBAEs raises toxicity concerns, lack tissue‐specific targeting capability limits clinical application. Herein, novel PBAE plasmid is constructed, which contains disulfide bonds backbone N‐acetylgalactosamine (GalNAc) moieties at terminals (GalNAc‐PBAEs). To address potential reduction nucleic acid condensing capacity caused by end‐capping with GalNAc, commonly amines conventional employed monomers create GalNAc‐PBAEs tertiary amine side chains. Through side‐chain screening, optimized GalNAc‐PBAE exhibits enhanced transfection efficiency, surpassing that top‐performing PBAE, C28‐E7, rivaling commercial reagent Lipo2000. Importantly, GalNAc enable plasmid‐PBAE polyplex efficiently target liver. In mouse model acute liver fibrosis, expression representative encoding HGF significantly mitigate fibrosis improve function, demonstrating designed therapy.

Language: Английский

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Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 10, 2025

Abstract The ability of small nucleic acids to modulate gene expression via a range processes has been widely explored. Compared with conventional treatments, acid therapeutics have the potential achieve long-lasting or even curative effects editing. As result recent technological advances, efficient delivery for therapeutic and biomedical applications achieved, accelerating their clinical translation. Here, we review increasing number classes most common chemical modifications platforms. We also discuss key advances in design, development application each platform. Furthermore, this presents comprehensive profiles currently approved drugs, including 11 antisense oligonucleotides (ASOs), 2 aptamers 6 siRNA summarizing modifications, disease-specific mechanisms action strategies. Other candidates whose trial status recorded updated are discussed. consider strategic issues such as important safety considerations, novel vectors hurdles translating academic breakthroughs clinic. Small produced favorable results trials address previously “undruggable” targets, suggesting that they could be useful guiding additional candidates.

Language: Английский

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Advances in the screening, diagnosis, and treatment of transthyretin amyloid cardiomyopathy: New insights and future directions

Trends in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Use of poly adenosine tail mimetics to enhance mRNA expression from genes associated with haploinsufficiency disorders

Molecular Therapy — Nucleic Acids, Journal Year: 2025, Volume and Issue: 36(1), P. 102453 - 102453

Published: Jan. 14, 2025

Language: Английский

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