Delivery of siRNA is a key hurdle to realizing the therapeutic promise of RNAi. By targeting internalizing cell surface antigens, antibody-siRNA complexes provide a possible solution. However, initial reports of antibody-siRNA complexes relied on non-specific charged interactions and have not been broadly applicable. To assess and improve this delivery method, we built on an industrial platform of therapeutic antibodies called THIOMABs, engineered to enable precise covalent coupling of siRNAs. We report that such coupling generates monomeric antibody-siRNA conjugates (ARCs) that retain antibody and siRNA activities. To broadly assess this technology, we generated a battery of THIOMABs against seven targets that use multiple internalization routes, enabling systematic manipulation of multiple parameters that impact delivery. We identify ARCs that induce targeted silencing in vitro and extend tests to target prostate carcinoma cells following systemic administration in mouse models. However, optimal silencing was restricted to specific conditions and only observed using a subset of ARCs. Trafficking studies point to ARC entrapment in endocytic compartments as a limiting factor, independent of the route of antigen internalization. Our broad characterization of multiple parameters using therapeutic-grade conjugate technology provides a thorough assessment of this delivery technology, highlighting both examples of success as well as remaining challenges.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333408 | PMC |
| http://dx.doi.org/10.1093/nar/gku1362 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Evaluating alignment of UK commercial baby food products with the WHO nutrient and promotion profile model.
Eur J Pediatr
January 2025
Nutritional Epidemiology Group, School of Food Science and Nutrition, University of Leeds, Leeds, UK.
Purpose: The first 1000 days of life are critical for long-term health outcomes, and there is increasing concern about the suitability of commercial food products for infants, toddlers, and children. This study evaluates the compliance of UK commercial baby food products with WHO Nutrient and Promotion Profile Model (NPPM) guidelines.
Methods: Between February and April 2023, data on 469 baby food products marketed for infants and children under 36 months were collected from the online platforms of four major UK supermarkets.
Adverse Pregnancy Outcomes in Patients with Polycystic Ovary Syndrome with Pre-Conceptional Hyperandrogenism: A Multi-Institutional Registry-Based Retrospective Cohort Study.
J Clin Med
December 2024
Department of Obstetrics and Gynecology and Women's Health, Taichung Veterans General Hospital, Taichung 407219, Taiwan.
: Women with polycystic ovarian syndrome (PCOS) are at higher risk for pregnancy complications. The PCOS population is heterogeneous, with different phenotypes linked to varying risks of adverse outcomes. However, literature on pre-conceptional hyperandrogenism is limited and based on small sample sizes.
View Article and Find Full Text PDFAn FPGA-Based SiNW-FET Biosensing System for Real-Time Viral Detection: Hardware Amplification and 1D CNN for Adaptive Noise Reduction.
Sensors (Basel)
January 2025
Department of Computer Science, Faculty of Sciences and Humanities Sciences, Majmaah University, Al Majmaah 11952, Saudi Arabia.
Impedance-based biosensing has emerged as a critical technology for high-sensitivity biomolecular detection, yet traditional approaches often rely on bulky, costly impedance analyzers, limiting their portability and usability in point-of-care applications. Addressing these limitations, this paper proposes an advanced biosensing system integrating a Silicon Nanowire Field-Effect Transistor (SiNW-FET) biosensor with a high-gain amplification circuit and a 1D Convolutional Neural Network (CNN) implemented on FPGA hardware. This attempt combines SiNW-FET biosensing technology with FPGA-implemented deep learning noise reduction, creating a compact system capable of real-time viral detection with minimal computational latency.
View Article and Find Full Text PDFA Survey of Deep Anomaly Detection in Multivariate Time Series: Taxonomy, Applications, and Directions.
Sensors (Basel)
January 2025
School of Computer Science, South China Normal University, Guangzhou 510555, China.
Multivariate time series anomaly detection (MTSAD) can effectively identify and analyze anomalous behavior in complex systems, which is particularly important in fields such as financial monitoring, industrial equipment fault detection, and cybersecurity. MTSAD requires simultaneously analyze temporal dependencies and inter-variable relationships have prompted researchers to develop specialized deep learning models to detect anomalous patterns. In this paper, we conducted a structured and comprehensive overview of the latest techniques in deep learning for multivariate time series anomaly detection methods.
View Article and Find Full Text PDFSynthesis of New Polyfluoro Oligonucleotides via Staudinger Reaction.
Int J Mol Sci
December 2024
Department of Physics, Novosibirsk State University, 2 Pirogov Str., Novosibirsk 630090, Russia.
Nowadays, nucleic acid derivatives capable of modulating gene expression at the RNA level have gained widespread recognition as promising therapeutic agents. A suitable degree of biological stability of oligonucleotide therapeutics is required for in vivo application; this can be most expeditiously achieved by the chemical modification of the internucleotidic phosphate group, which may also affect their cellular uptake, tissue distribution and pharmacokinetics. Our group has previously developed a strategy for the chemical modification of the phosphate group via the Staudinger reaction on a solid phase of the intermediate dinucleoside phosphite triester and a range of, preferably, electron deficient organic azides such as sulfonyl azides during automated solid-phase DNA synthesis according to the conventional β-cyanoethyl phosphoramidite scheme.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!