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Clinical pharmacology of siRNA therapeutics: current status and future prospects
Expert Rev Clin Pharmacol. 2022 Oct 17. doi: 10.1080/17512433.2022.2136166. Online ahead of print.ABSTRACTINTRODUCTION: Small interfering RNA (siRNA) has emerged as a powerful tool for post-transcriptional downregulation of multiple genes for various therapies. Naked siRNA molecules are surrounded by several barriers that tackle their optimum delivery to target tissues such as limited cellular uptake, short circulation time, degradation by endonucleases, glomerular filtration, and capturing by the reticuloendothelial system (RES).AREAS COVERED: This review provides insights into studies that investigate various siRNA-based...
Source: Expert Review of Clinical Pharmacology - October 17, 2022 Category: Drugs & Pharmacology Authors: Ahmed Khaled Abosalha Jacqueline Boyajian Waqar Ahmad Paromita Islam Merry Ghebretatios Sabrina Schaly Rahul Thareja Karan Arora Satya Prakash Source Type: research

Molecules, Vol. 28, Pages 2191: Potential of siRNA-Bearing Subtilosomes in the Treatment of Diethylnitrosamine-Induced Hepatocellular Carcinoma
grawal Mohammad Owais Therapeutics, based on small interfering RNA (siRNA), have demonstrated tremendous potential for treating cancer. However, issues such as non-specific targeting, premature degradation, and the intrinsic toxicity of the siRNA, have to be solved before they are ready for use in translational medicines. To address these challenges, nanotechnology-based tools might help to shield siRNA and ensure its specific delivery to the target site. Besides playing a crucial role in prostaglandin synthesis, the cyclo-oxygenase-2 (COX-2) enzyme has been reported to mediate carcinogenesis in various types of canc...
Source: Molecules - February 27, 2023 Category: Chemistry Authors: Fauzia Jamal Ghufran Ahmed Mohammad Farazuddin Ishrat Altaf Saba Farheen Qamar Zia Asim Azhar Hira Ahmad Aijaz Ahmed Khan Satyanarayana Somavarapu Anshu Agrawal Mohammad Owais Tags: Article Source Type: research

Where should siRNAs go: applicable organs for siRNA drugs
Exp Mol Med. 2023 Jul 10. doi: 10.1038/s12276-023-00998-y. Online ahead of print.ABSTRACTRNA interference mediated by small interfering RNAs (siRNAs) has been exploited for the development of therapeutics. siRNAs can be a powerful therapeutic tool because the working mechanisms of siRNAs are straightforward. siRNAs determine targets based on their sequence and specifically regulate the gene expression of the target gene. However, efficient delivery of siRNAs to the target organ has long been an issue that needs to be solved. Tremendous efforts regarding siRNA delivery have led to significant progress in siRNA drug developm...
Source: Molecular Medicine - July 10, 2023 Category: Molecular Biology Authors: Insook Ahn Chanhee S Kang Jinju Han Source Type: research

pH-Responsive Dynaplexes as Potent Apoptosis Inductors by Intracellular Delivery of Survivin siRNA
Biomacromolecules. 2023 Jul 31. doi: 10.1021/acs.biomac.3c00424. Online ahead of print.ABSTRACTGene knockdown by siRNA offers an unrestricted choice of targets and specificity based on the principle of complementary Watson-Crick base pairing with mRNA. However, the negative charge, large molecular size, and susceptibility to enzymatic degradation of siRNA impede its successful transfection, hence limiting its potential for therapeutic use. The development of efficient and safe siRNA transfection agents is, therefore, critical for siRNA-based therapy. Herein, we developed a protein-based biodynamic polymer (biodynamer) that...
Source: Biomacromolecules - July 31, 2023 Category: Biochemistry Authors: Yun Liu Salma Ashmawy Lorenz Latta Agnes-Valencia Weiss Alexander F Kiefer Sarah Nasr Brigitta Loretz Anna K H Hirsch Sangeun Lee Claus-Michael Lehr Source Type: research

Development of siRNA delivery strategy by active control of tumor microenvironment.
Abstract Efficient systemic siRNA delivery to cells in the target tissue is a current critical challenge in the drug delivery field. Several studies have demonstrated that nanoparticles such as polyethylene glycol (PEG)-coated siRNA-lipoplexes may enhance the systemic delivery of siRNA to tumor. However, the disordered tumor microenvironment still poses a potential impediment with respect to the efficient delivery of PEG-coated siRNA-lipoplexes. We recently showed that metronomic S-1 dosing (daily oral administration) enhanced the accumulation of PEG-coated liposome containing anticancer drug in solid tumor tissue...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 25, 2013 Category: Drugs & Pharmacology Authors: Ishida T, Kiwada H Tags: Yakugaku Zasshi Source Type: research

Adenovirus-mediated expression of bone morphogenetic protein-2 activates titanium particle-induced osteoclastogenesis and this effect occurs in spite of the suppression of TNF-α expression by siRNA.
In this study, we constructed an adenoviral vector carrying TNF‑small interfering RNA (siRNA) (Ad‑TNF‑siRNA), as well as a vector carrying both the BMP‑2 gene and TNF‑α‑siRNA (Ad-BMP‑2‑TNF‑siRNA). The two adenoviral vectors significantly suppressed the expression of TNF-α; however, only treatment with Ad-TNF-siRNA significantly inhibited osteoclastogenesis. We demonstrate that the overexpression of BMP‑2, despite the suppression of TNF‑α expression by Ad-BMP‑2‑TNF‑siRNA, increases the size and number of titanium (Ti) particle‑induced multinuclear osteoclasts, the expression of osteoclast g...
Source: International Journal of Molecular Medicine - May 27, 2013 Category: Molecular Biology Authors: Sun S, Guo H, Zhang J, Yu B, Sun K, Jin Q Tags: Int J Mol Med Source Type: research

siRNA enhances DNA-mediated interferon lambda-1 response through crosstalk between RIG-I and IFI16 signalling pathway
In addition to silencing specific genes, small interfering RNA (siRNA) transfection is also associated with the non-specific induction of inflammatory cytokines and type I interferon. Those so-called "off-target" effects have considerable implications for the interpretation of in vitro studies and clinical application of siRNA. The present study attempted to develop a better understanding of the mechanism involved in these off target effects. Synthesized siRNA significantly enhances DNA-mediated interferon lambda-1 response (IFN-1/IL-29), a newly characterized antiviral interferon in non-immune or primary immune cells. Thi...
Source: Nucleic Acids Research - December 28, 2013 Category: Research Authors: Sui, H., Zhou, M., Chen, Q., Lane, H. C., Imamichi, T. Tags: RNA Source Type: research

Polymeric micelles containing reversibly phospholipid-modified anti-survivin siRNA: A promising strategy to overcome drug resistance in cancer
Highlights: Abstract: The discovery that survivin, a small anti-apoptotic protein, is involved in chemoresistance, opens a new scenario to overcome the drug resistance in cancer. It was shown that siRNA can efficiently inhibit the expression of survivin in cancer cells. However, the clinical use of siRNA is still hampered by an unfavorable pharmacokinetic profile. To address this problem, earlier we developed a novel system to deliver siRNA into cancer cells. Namely, we reversibly modified the survivin siRNA with a phosphothioethanol (PE) portion via a reducible disulfide bond and incorporated the resulting siRNA-S-S-PE co...
Source: Cancer Letters - October 21, 2013 Category: Cancer & Oncology Authors: G. Salzano, R. Riehle, G. Navarro, F. Perche, G. De Rosa, V.P. Torchilin Tags: Research Articles Source Type: research

Superparamagnetic iron oxide nanoparticles mediated 131I-hVEGF siRNA inhibits hepatocellular carcinoma tumor growth in nude mice
Conclusions: EMF-guided 131I-hVEGF siRNA/SilenceMag exhibited an antitumor effect. The synergic therapy of 131I-hVEGF siRNA/SilenceMag might be a promising future treatment option against HCC with the dual functional properties of tumor therapy and imaging.
Source: BMC Cancer - February 21, 2014 Category: Cancer & Oncology Authors: Jing ChenShu ZhuLiangqian TongJiansha LiFei ChenYunfeng HanMing ZhaoWei Xiong Source Type: research

Targeted siRNA-immunoliposomes as a promising therapeutic agent against highly pathogenic avian influenza A (H5N1) virus infection.
This study describes a proof of concept study on the use of siRNA-immunoliposomes as a therapeutic agent against H5N1 influenza virus infection. SiRNA specific for influenza virus nucleoprotein (NP) mRNA was employed as the key antiviral agent to inhibit viral replication in this study. A humanized single-chain Fv antibody (huscFv) against the hemagglutinin (HA) of H5N1 highly pathogenic avian influenza (HPAI) was used as the targeting molecule to HA of H5N1 virus, which is abundantly expressed on the surface of infected cells. The huscFv was decorated onto cationic PEGylated DC-Chol/DOPE liposomes to generate immunoliposo...
Source: Antimicrobial Agents and Chemotherapy - March 10, 2014 Category: Microbiology Authors: Khantasup K, Kopermsub P, Chaichoun K, Dharakul T Tags: Antimicrob Agents Chemother Source Type: research