Overcoming endosomal/lysosomal barriers: Advanced strategies for cytosolic siRNA delivery DOI
Yulin Deng,

Mengxi Zhu,

Xiwen Hu

et al.

Chinese Chemical Letters, Journal Year: 2024, Volume and Issue: unknown, P. 110736 - 110736

Published: Dec. 1, 2024

Language: Английский

Natural, modified and conjugated carbohydrates in nucleic acids DOI Creative Commons
Debashis Dhara, Laurence A. Mulard, Marcel Hollenstein

et al.

Chemical Society Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

The deep interconnection between nucleic acids and carbohydrates has prompted numerous synthetic campaigns to understand acid etiology, develop orthogonal genetic systems, improve the properties of therapeutic oligonucleotides.

Language: Английский

Citations

2
Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications DOI Creative Commons
Yingying Shi,

Miaoyuan Shi,

Yì Wáng

et al.

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

Published: Nov. 14, 2024

Abstract In the last decade, messenger ribonucleic acid (mRNA)-based drugs have gained great interest in both immunotherapy and non-immunogenic applications. This surge can be largely attributed to demonstration of distinct advantages offered by various mRNA molecules, alongside rapid advancements nucleic delivery systems. It is noteworthy that immunogenicity presents a double-edged sword. context immunotherapy, extra supplementation adjuvant generally required for induction robust immune responses. Conversely, non-immunotherapeutic scenarios, activation unwanted considering host tolerability high expression demand mRNA-encoded functional proteins. Herein, mainly focused on linear non-replicating mRNA, we overview preclinical clinical progress prospects medicines encompassing vaccines other therapeutics. We also highlight importance focusing host-specific variations, including age, gender, pathological condition, concurrent medication individual patient, maximized efficacy safety upon administration. Furthermore, deliberate potential challenges may encounter realm disease treatment, current endeavors improvement, as well application future advancements. Overall, this review aims present comprehensive understanding mRNA-based therapies while illuminating prospective development drugs.

Language: Английский

Citations

11
Small RNA and Toll-like receptor interactions: origins and disease mechanisms DOI
Jiancheng Yu, Xu Dong Zhang, Chen Cai

et al.

Trends in Biochemical Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

1
RNA and condensates: Disease implications and therapeutic opportunities DOI Creative Commons

Tina W. Han,

Bede Portz,

Richard A. Young

et al.

Cell chemical biology, Journal Year: 2024, Volume and Issue: 31(9), P. 1593 - 1609

Published: Sept. 1, 2024

Language: Английский

Citations

6
Amide Internucleoside Linkages Suppress the MicroRNA-like Off-Target Activity of Short Interfering RNA DOI
Chandan Pal, Michael Richter,

J.C. Harasgama

et al.

ACS Chemical Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

RNA interference (RNAi) has rapidly matured as a novel therapeutic approach. In this field, chemical modifications have been critical to the clinical success of short interfering RNAs (siRNAs). Notwithstanding significant advances, achieving robust durability and gene silencing in extrahepatic tissues, well reducing off-target effects siRNA, are areas where can still improve siRNA performance. The present study developed challenging synthesis amide-linked guanosine dimers (GAM1G GAM1A) completed an "amide walk" one by one, systematically replacing every internucleoside phosphate with amide linkage guide strand targeting PIK3CB gene. Dual-luciferase RT-qPCR assays HeLa cells showed that, model system unmodified siRNAs, at position 3 (between nucleosides 4) suppressed cleavage YY1 FADD mRNAs similarly industry gold standard modification glycol nucleic acid (GNA). These results suggest that linkages seed region strong potential specificity siRNAs suppressing microRNA-like activity.

Language: Английский

Citations

0
The time course of in vivo cellular responses to LNPs DOI Creative Commons
David Loughrey, Kalina Paunovska, Elisa Schrader Echeverri

et al.

Chemical Communications, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Transcriptomic analysis undertaken at different timepoints can shed light on mRNA-LNP in vivo delivery dynamics.

Language: Английский

Citations

0
General Platform for Efficient and Modular Assembly of GalNAc–siRNA Conjugates via Primary Amines and o-Nitrobenzyl Alcohol Cyclization Photoclick Chemistry Enabling Rapid Access to Therapeutic Oligonucleotides DOI Creative Commons

Hui-Jun Nie,

Hao Hu, Xinming Qi

et al.

JACS Au, Journal Year: 2025, Volume and Issue: 5(3), P. 1402 - 1412

Published: Feb. 24, 2025

Oligonucleotide-based therapies, especially ligand-conjugated siRNAs, offer significant therapeutic potential for a wide array of diseases. However, conventional solid-phase synthesis and current postsynthetic in-solution conjugation methods face notable challenges related to efficiency, accessibility, the scalability diverse ligand–oligonucleotide conjugates. Herein, we introduce novel strategy highly efficient, rapid, modular assembly GalNAc–siRNA conjugates based on light-induced primary amine o-nitrobenzyl alcohol cyclization (PANAC) chemistry. Leveraging advantages PANAC photoclick chemistry linkers, our method enables direct trivalent GalNAc (tGalNAc) with commercially available primary-amine-modified siRNAs. This approach demonstrates efficient rapid therapeutically relevant oligonucleotides ligands interest, offering operational simplicity practicality; thus, it effectively overcomes limitations existing methods. More importantly, developed siRNA–tGalNAc showed robust gene silencing effect superior parent siRNA conjugate, highlighting effectiveness in generating screening enhance vivo potency. Overall, oligonucleotide–tGalNAc using readily accessible tGalNAc-amine ligands. expands toolkit conjugates, providing general platform broad applicability, thereby advancing optimization development oligonucleotide-based therapeutics.

Language: Английский

Citations

0
Unravelling the Regulatory Roles of lncRNAs in Melanoma: From Mechanistic Insights to Target Selection DOI Open Access

Beatrice Moras,

Claudia Sissi

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2126 - 2126

Published: Feb. 27, 2025

Melanoma is the deadliest form of skin cancer, and its treatment poses significant challenges due to aggressive nature resistance conventional therapies. Long non-coding RNAs (lncRNAs) represent a new frontier in search for suitable targets control melanoma progression invasiveness. Indeed, lncRNAs exploit wide range regulatory functions along chromatin remodeling, gene transcription, post-transcription, transduction, post-transduction ultimately tune multiple cellular processes. The understanding this intricate flexible network orchestrated by pathological conditions can strategically support rational identification promising targets, speeding up setup therapeutics integrate currently available approaches. Here, most recent findings on involved will be analyzed. In particular, functional links between their mechanisms action some frequently underestimated features, like different subcellular localizations, highlighted.

Language: Английский

Citations

0
Leveraging Knowledge Networks: Rethinking Technological Value Distribution in Mrna Vaccine Innovations DOI
Rossana Mastrandrea, Fabio Montobbio, Gabriele Pellegrino

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
METTL3 promotes infantile pneumonia-induced lung injury by the m6A-TBL1XR1-ACSL1 axis DOI

Fuxing Song,

Fang Guo, Bo Su

et al.

Cellular Immunology, Journal Year: 2025, Volume and Issue: 411-412, P. 104944 - 104944

Published: March 16, 2025

Language: Английский

Citations

0