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Nanoparticle-Mediated Small RNA Deliveries for Molecular Therapies
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Ramasamy Paulmurugan, Uday Kumar Sukumar, Tarik F. Massoud
MiRNAs are small single stranded RNAs of 18–23 nucleotides that are partially or fully complimentary to the 3’ non-coding region of target mRNA sequence. MiRNAs achieve gene silencing through blocking mRNA translation or by degrading target mRNAs. The ability to achieve sequence-specific gene silencing using RNAi (siRNA, shRNA, and miRNA) has been used in a wide range of applications, including the treatment of numerous diseases, particularly for the cancer therapy [91]. Nevertheless, in vivo systemic administration and delivery of the small silencing RNA-based therapeutics to cells and tumors remain a challenge, owing to limitations such as poor cellular uptake, degradation by serum nucleases, and rapid renal clearance after administration [92]. To overcome these limitations, the development of effective and safe nanocarriers for systemic delivery of small silencing RNAs is required for efficient cancer therapy. Biodegradable polymer nanoparticles have been found to be safe and effective nanocarriers for the delivery of small silencing RNAs and show promising translational clinical applications.
RNAi as New Class of Nanomedicines
Published in Dan Peer, Handbook of Harnessing Biomaterials in Nanomedicine, 2021
Monika Dominska, Derek M. Dykxhoorn
RNA interference (RNAi)-based gene-silencing technologies provide a novel approach for the treatment of a variety of diseases through the sequence-specific silencing of gene expression. The application of small interfering RNA (siRNA) as potential therapeutic agents requires the development of clinically feasible delivery strategies that enhance their pharmacological properties. To be effective, siRNAs must be delivered to and taken up by specific target cells and tissues, enter the cytoplasm, and associate with the RNA-induced silencing complex (RISC) to guide the sequence-specific cleavage of appropriate messenger RNA (mRNA). This chapter will focus on recent progress made in the development of safe and effective therapeutic strategies for the siRNA-based silencing of gene expression.
Nanomedicinal Genetic Manipulation: Promising Strategy to Treat Some Genetic Diseases
Published in Sarwar Beg, Mahfoozur Rahman, Md. Abul Barkat, Farhan J. Ahmad, Nanomedicine for the Treatment of Disease, 2019
Biswajit Mukherjee, Iman Ehsan, Debasmita Dutta, Moumita Dhara, Lopamudra Dutta, Soma Sengupta
Improved understanding of the diversity of the human genome now enables us to understand the possible cause of various rare genetic diseases like cancer, diabetes, hypertension, obesity, and anemia. Suitable nanocarriers are required to overcome challenges such as cellular uptake and pharmacokinetics. Nanotechnology is one of the most promising fields in medical science to meet this type of expected progress and benefits. A range of therapeutic advantages of Nanomedicine over conventional therapy certainly is a revolution in medical science. Gene silencing technology plays the major role in the treatment of various genetic diseases. siRNA technology is being utilized and developing very fast from preclinical to clinical trial level. It might be the most successful tool for early-stage diagnosis to effective treatment for genetic diseases. In conclusion, nano-medicine is a premise for future research on the benefits and applicability of nanotechnology in medicine to treat chronic genetic diseases.
Benzo[a]pyrene osteotoxicity and the regulatory roles of genetic and epigenetic factors: A review
Published in Critical Reviews in Environmental Science and Technology, 2022
Jiezhang Mo, Doris Wai-Ting Au, Jiahua Guo, Christoph Winkler, Richard Yuen-Chong Kong, Frauke Seemann
MiRNAs serve an important role in RNA silencing and the posttranscriptional regulation of gene expression. They consist of small, single-stranded RNA that are normally 18–22 nucleotides in length. MiRNAs regulate target gene silencing by completely or partly complementary binding to the 3′-untranslated regions (3′-UTRs), 5′-untranslated regions (5′-UTRs), and/or gene coding regions (CDS) of target mRNAs, which leads to translational repression or degradation of the target transcripts (mRNA cleavage) (Ha & Kim, 2014; Liu & Paroo, 2010). Numerous studies have shown that miRNAs are heavily involved in the regulation of bone modeling and remodeling in mammals (Huang et al., 2010; Liao et al., 2013; Mizoguchi et al., 2010; Sugatani & Hruska, 2009; Wang, Chung, et al., 2013) and are important regulators of bone formation and resorption, such as essential transcription factors (like RUNX2, OSX, ATF4, C-FOS and NFATc1), developmental signaling pathways (e.g., the Bmp, Wnt and Rankl-Rank-OPG pathways) and other signaling pathways associated with growth factor-mediated kinases (Hrdlicka et al., 2019; Kim & Lim, 2014).
Applications and hazards associated with carbon nanotubes in biomedical sciences
Published in Inorganic and Nano-Metal Chemistry, 2020
Ali Hassan, Afraz Saeed, Samia Afzal, Muhammad Shahid, Iram Amin, Muhammad Idrees
Small interfering RNA(RNAi) is a process of gene silencing at co-transcriptional level triggered by micro RNA and small interfering RNA.[65] Due to gene silencing ability, RNAi has applications in gene therapy. Small RNA encoding extracellular signal-regulated kinase was delivered to cardiomyocyte cells by using functional SWCNTs. The result obtained with approximately 75% knockdown of extracellular signal-regulated kinase target protein.[66] In chemically functionalized CNTs, negatively charge small RNA condense successfully with the amino group of CNTs. This reduces the need for linker molecules and transports small RNA inside the cell efficiently which then down-regulate the expression of target gene significantly.[67]
Preparation and characterization of novel albumin-sericin nanoparticles as siRNA delivery vehicle for laryngeal cancer treatment
Published in Preparative Biochemistry and Biotechnology, 2019
Eda Yalcin, Goknur Kara, Ekin Celik, Ferda Alpaslan Pinarli, Guleser Saylam, Ceren Sucularli, Serhat Ozturk, Esin Yilmaz, Omer Bayir, Mehmet Hakan Korkmaz, Emir Baki Denkbas
RNA interference (RNAi) has become a widely used powerful tool in gene functional analyses and therapeutic applications since it has first emerged as a post-transcriptional gene silencing strategy in 1998.[1,2] This process provides sequence-specific degradation of the target mRNA and hence inhibits translation of the target protein via the key role of siRNA. In this mechanism, the double-stranded RNAs (dsRNAs) are cleaved by the enzyme called Dicer and divided into fragments of 21–23 nucleotides which are called siRNAs. These siRNAs, consisting of a passenger strand and a guide strand, bind to the RNA-Induced Silencing Complex (RISC). Subsequently, the guide strand is complementarily directed to the target mRNA by the activity of Argonaute-2 enzyme to cleave between the 10th and 11th bases of the mRNA.[3] siRNAs can be also produced synthetically with unique sequences that are highly specific to the target. siRNAs have been studied commonly for cancer treatment owing to their high potency for gene silencing.[4] Despite this great potential, a number of drawbacks must be considered for its therapeutic use. The difficulty in delivery of the siRNA molecule to the targeted area resulting from its rapid enzymatic degradation and insufficient cellular uptake is the major obstacle.[4] Therefore, an efficient carrier is still a need in siRNA therapies, and lately, nanoparticles have come forward as favorable delivery systems for safe siRNA transportation and accomplishment of effective gene knockdown in targeted cells.