Prediction of exosomal miRNA-based biomarkers for liquid biopsy DOI Creative Commons
Akanksha Arora, Gajendra P. S. Raghava

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 21, 2024

Abstract In this study, we investigated the properties of exosomal miRNAs to identify potential biomarkers for liquid biopsy. We collected 956 and non-exosomal miRNA sequences from RNALocate miRBase develop predictive models. Our initial analysis reveals that specific nucleotides are preferred at certain positions in associated with exosomes. employed an alignment-based approach, artificial intelligence (AI) models, ensemble methods predicting miRNAs. For used a motif-based method MERCI similarity-based BLAST, achieving high precision but low coverage about 29%. The AI developed using machine learning, deep learning techniques, large language achieved maximum AUC 0.707 MCC 0.268 on independent dataset. Finally, our method, combining AI-based reached 0.73 0.352 have web server, EmiRPred, assist scientific community designing identifying motifs ( https://webs.iiitd.edu.in/raghava/emirpred/ ). Key points Exosomal applications biopsy An has been predict design array models were built approaches (ML, DL, LLM) A variety important features identified webserver, python package, github, standalone software created

Language: Английский

Extracellular Vesicles: A New Star for Gene Drug Delivery DOI Creative Commons

Man Sun,

Huan Zhang, Jiayi Liu

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 2241 - 2264

Published: March 1, 2024

Abstract: Recently, gene therapy has become a subject of considerable research and been widely evaluated in various disease models. Though it is considered as stand-alone agent for COVID-19 vaccination, still suffering from the following drawbacks during its translation bench to bedside: high sensitivity exogenous nucleic acids enzymatic degradation; severe side effects induced either by or components formulation; difficulty cross barriers before reaching therapeutic target. Therefore, successful application therapy, safe reliable transport vector urgently needed. Extracellular vesicles (EVs) are ideal candidate delivery drugs owing their low immunogenicity, good biocompatibility toxicity. To better understand properties EVs advantages drug vehicles, this review covers origin methods generation, well common isolation purification research, with pros cons discussed. Meanwhile, engineering also highlighted. In addition, paper presents progress EVs-mediated microRNAs, small interfering RNAs, messenger plasmids, antisense oligonucleotides. We believe will provide theoretical basis development drugs. Keywords: extracellular vesicles, system,

Language: Английский

Citations

12
Genetically engineered loaded extracellular vesicles for drug delivery DOI

Zuriñe Erana-Perez,

Manoli Igartúa, Edorta Santos‐Vizcaíno

et al.

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(4), P. 350 - 365

Published: March 19, 2024

Language: Английский

Citations

11
CRISPR-Cas9 Gene Therapy: Non-Viral Delivery and Stimuli-Responsive Nanoformulations DOI Creative Commons
Hyun-Woo Lee, Won‐Yeop Rho,

Yoon-Hee Kim

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(3), P. 542 - 542

Published: Jan. 24, 2025

The CRISPR-Cas9 technology, one of the groundbreaking genome editing methods for addressing genetic disorders, has emerged as a powerful, precise, and efficient tool. However, its clinical translation remains hindered by challenges in delivery efficiency targeting specificity. This review provides comprehensive analysis structural features, advantages, potential applications various non-viral stimuli-responsive systems, examining recent progress to emphasize address these limitations advance therapeutics. We describe how reports that nonviral vectors, including lipid-based nanoparticles, extracellular vesicles, polymeric gold mesoporous silica can offer diverse advantages enhance stability, cellular uptake, biocompatibility, based on their structures physio-chemical stability. also summarize nanoformulations, type vector, introduce precision control delivery. Stimuli-responsive nanoformulations are designed respond pH, redox states, external triggers, facilitate controlled targeted delivery, minimize off-target effects. insights our suggest future gene therapy technologies highlight systems CRISPR-Cas9’s efficacy, positioning them pivotal tools gene-editing therapies.

Language: Английский

Citations

1
Recent advances and future prospects of engineered exosomes as advanced drug and gene delivery systems DOI
Waleed Y. Rizg, Majed Alghamdi, Sherif El Saadany

et al.

Journal of Drug Delivery Science and Technology, Journal Year: 2025, Volume and Issue: 106, P. 106696 - 106696

Published: Feb. 6, 2025

Language: Английский

Citations

1
The Plethora of RNA–Protein Interactions Model a Basis for RNA Therapies DOI Open Access

Stephen Dansereau,

Hua Cui,

Ricky Dartawan

et al.

Genes, Journal Year: 2025, Volume and Issue: 16(1), P. 48 - 48

Published: Jan. 2, 2025

The notion of RNA-based therapeutics has gained wide attractions in both academic and commercial institutions. RNA is a polymer nucleic acids that been proven to be impressively versatile, dating its hypothesized World origins, evidenced by enzymatic roles facilitating DNA replication, mRNA decay, protein synthesis. This underscored through the activities riboswitches, spliceosomes, ribosomes, telomerases. Given broad range interactions within cell, can targeted therapeutic or modified as pharmacologic scaffold for diseases such nucleotide repeat disorders, infectious diseases, cancer. techniques have researched include, but are not limited to, CRISPR/Cas gene editing, anti-sense oligonucleotides (ASOs), siRNA, small molecule treatments, aptamers. knowledge gleaned from studying RNA-centric mechanisms will inevitably improve design therapeutics. Building on this understanding, we explore physiological diversity functions, examine specific dysfunctions, splicing errors viral interactions, discuss their implications.

Language: Английский

Citations

0
Rescue of the disease-associated phenotype in CRISPR-corrected hiPSCs as a therapeutic approach for inherited retinal dystrophies DOI Creative Commons

Laura Siles,

Esther Pomares

Molecular Therapy — Nucleic Acids, Journal Year: 2025, Volume and Issue: 36(1), P. 102482 - 102482

Published: Feb. 11, 2025

Inherited retinal dystrophies (IRDs), such as retinitis pigmentosa and Stargardt disease, are a group of rare diseases caused by mutations in more than 300 genes that currently have no treatment most cases. They commonly trigger blindness other ocular affectations due to cell degeneration. Gene editing has emerged promising powerful strategy for the development IRD therapies, allowing permanent correction pathogenic variants. Using clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 transcription activator-like effector nucleases (TALEN) gene-editing tools, we precisely corrected seven hiPS lines derived from patients carrying ABCA4, BEST1, PDE6A, PDE6C, RHO, or USH2A. Homozygous point insertions/deletions resulted highest homology-directed repair efficiencies, with at least half clones repaired properly without off-target effects. Strikingly, heterozygous variant was achieved using wild-type allele patient template DNA repair. These results suggest unexpected potential application CRISPR donor template-free single-nucleotide modifications. Additionally, exhibited reversion disease-associated phenotype cellular models. data strengthen study gene editing-based approaches treatment.

Language: Английский

Citations

0
Click chemistry-based modified exosomes: Towards enhancing precision in cancer theranostics DOI Creative Commons
Nobendu Mukerjee, Swastika Maitra, Mandeep Kaur

et al.

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: unknown, P. 160915 - 160915

Published: Feb. 1, 2025

Language: Английский

Citations

0
CRISPR-Cas9 Gene Editing for Targeting Cancer Stem Cells in Glioblastoma Multiforme DOI

Saifullah Khan Mahar,

Ali Amara,

Ammara Ali

et al.

Indus journal of bioscience research., Journal Year: 2025, Volume and Issue: 3(2), P. 394 - 407

Published: Feb. 28, 2025

This research investigates the possibility of CRISPR-Cas9 gene editing in targeting glioblastoma multiforme (GBM) cancer stem cells (CSCs) for increasing CSC sensitivity to conventional treatments and suppressing tumor growth. A quantitative method was used, with a sample 36 GBM patients diagnosed treated at major tertiary care centers Pakistan, namely Aga Khan University Hospital (Karachi), Shaukat Khanum Memorial Cancer (Lahore), Pakistan Institute Medical Sciences (Islamabad). Tumor tissue samples were obtained time surgical resection processed harvest CSCs based on certain markers like CD133 Nestin using fluorescence-activated cell sorting (FACS). The subsequently conducted isolated knock out genes interest involved stemness therapy resistance, such as SOX2, MGMT, Wnt/β-catenin. efficacy evaluated by pre- post-CRISPR growth rates, proliferation assays vitro, neurosphere formation. Multiple regression analysis showed that greatly enhanced (B = 1.427, p 0.000), pre-CRISPR rate -0.512, 0.009) initial size -0.312, 0.040) having negative correlation treatment. Moreover, increased MGMT expression 0.050) related decreased sensitivity. ANOVA test significant variability among efficacies different delivery methods CRISPR-Cas9, including viral vectors, nanoparticles, electroporation (F 4.56, 0.008), pointed towards optimizing strategies achieve efficient editing. shows promise treatment, but issues off-target effects need resolution enable future clinical applications.

Language: Английский

Citations

0
Extracellular vesicles for the delivery of gene therapy DOI
Emilio Di Ianni,

Wataru Obuchi,

Koen Breyne

et al.

Nature Reviews Bioengineering, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Language: Английский

Citations

0
Exosomes in Precision Oncology and Beyond: From Bench to Bedside in Diagnostics and Therapeutics DOI Open Access

Emile M. Youssef,

Dannelle Palmer,

Brandon Fletcher

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(6), P. 940 - 940

Published: March 10, 2025

Exosomes have emerged as pivotal players in precision oncology, offering innovative solutions to longstanding challenges such metastasis, therapeutic resistance, and immune evasion. These nanoscale extracellular vesicles facilitate intercellular communication by transferring bioactive molecules that mirror the biological state of their parent cells, positioning them transformative tools for cancer diagnostics therapeutics. Recent advancements exosome engineering, artificial intelligence (AI)-driven analytics, isolation technologies are breaking barriers scalability, reproducibility, clinical application. Bioengineered exosomes being leveraged CRISPR-Cas9 delivery, while AI models enhancing biomarker discovery liquid biopsy accuracy. Despite these advancements, key obstacles heterogeneity populations lack standardized protocols persist. This review synthesizes pioneering research on biology, molecular translation, emphasizing dual roles both mediators tumor progression intervention. It also explores emerging areas, including microbiome–exosome interactions integration machine learning exosome-based medicine. By bridging innovation with translational strategies, this work charts a forward-looking path integrating into next-generation care, setting it apart comprehensive guide overcoming technological hurdles rapidly evolving field.

Language: Английский

Citations

0