China
Africa
Explore chapters and articles related to this topic
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
The miRNAs are small, highly conserved, non-coding RNAs of 18–24 nucleotides in length endogenously expressed in cells that are engaged in the post transcriptional regulation of gene expression through the RNAi pathway [16, 89, 91–94, 113–118]. The miRNA expression is dysregulated in cellular diseases including cancer, where miRNA expressions are closely associated with cancer development, growth, invasion, and metastasis [16, 89, 91–94, 113–118]. Based on their functions, they are categorized as oncogenic miRNAs (oncomiRs) and tumor suppressor miRNAs. OncomiRs promote tumor growth by inhibiting tumor suppressor and apoptotic genes, whereas anti-oncomiRs block the function of proteins involved in cell cycle and apoptosis [93, 116]. There are numerous miRNAs that are reported to be tumor suppressors (miR-17-5p, miR-21, miR-29, miR-34, miR-127, miR-155, let-7, etc.) [115]. This list has been growing, and it is expected that there may be many more miRNAs with important functions yet to be discovered. Recently, we and several other groups have been investigating miRNAs as a new class of molecularly targeted anticancer therapeutics [4, 5].
siRNA Delivery for Therapeutic Applications Using Nanoparticles
Published in Yashwant Pathak, Gene Delivery, 2022
Recently, the potential application of RNA interference (RNAi) has drawn central attention in siRNA delivery. RNAi is the term given to the ability of a double- RNA-induced silencing (RISC) complex stranded RNA (dsRNA) containing a homologous sequence to a specific gene, leading to sequence-specific gene silencing [8]. RNAi is an endogenous post-transcriptional regulation process that consists of small regulatory RNAs, including microRNAs (miRNAs) or small interfering RNAs (siRNAs) that are able to silence target messenger RNAs (mRNAs) in a sequence-specific procedure. After the discovery of RNAi in Caenorhabditis elegans and subsequent demonstration of siRNA activity in mammalian cells, RNAi has received considerable attention as an effective therapy for multiple diseases like cancer and viral infections, particularly for those diseases with “undruggable” molecular targets [9, 10].
Cross Talk Between Heat Shock and Oxidative Stress Inducible Genes During Myocardial Adaptation to Ischemia
Published in John J. Lemasters, Constance Oliver, Cell Biology of Trauma, 2020
Dipak K. Das, Nilanjana Maulik
Although the aforementioned adaptation techniques have been proven beneficial against ischemia reperfusion, the precise mechanism of adaptation remains unknown. Many questions remain unanswered. Are these adaptations interrelated? Most of the stress adaptations cause synthesis of heat shock proteins and/or oxidative stress-inducible proteins. Is there a common link? Stress adaptation also results in the induction of genes. How does the post-transcriptional regulation occur? To answer some of these questions, the heart was adapted to stress by three different methods, ischemic stress, oxidative stress, and heat shock. The results of myocardial adaptation to ischemia were compared by examining the induction of the gene expression and by studying the antioxidant status of the heart and myocardial performance during ischemia and reperfusion following adaptation.
Epigenetic modulations in cancer: predictive biomarkers and potential targets for overcoming the resistance to topoisomerase I inhibitors
Published in Annals of Medicine, 2023
Moustafa M. Madkour, Wafaa S. Ramadan, Ekram Saleh, Raafat El-Awady
MicroRNAs (miRNAs) are a class of small ncRNAs, which function in post-transcriptional regulation of gene expression. They are powerful regulators of various cellular activities including cell growth, differentiation, development and apoptosis. Therefore, they have been linked to many diseases, including cancer [122,123]. Interestingly, miRNAs were found to directly affect Top I expression in cancer cells. For example, miR-23a and miR-139 were found to inhibit Top I expression in hepatocellular carcinoma (HCC). These miRNAs were reported to bind directly to the 3′ untranslated region (UTR) of Top I mRNA and to suppress the expression of the corresponding protein. Thus, the inhibition of miR-23a or miR-139 further augments Top I expression (Figure 4(A)). The fact that forced overexpression of these miRNAs might attenuate the cytotoxicity of Top I poisons through Top I downregulation further demonstrates the link between miRNAs and Top I. These findings indicate that Top I is a direct target of miR-23a and miR-139 [124,125].
Tight junctions: from molecules to gastrointestinal diseases
Published in Tissue Barriers, 2023
Aekkacha Moonwiriyakit, Nutthapoom Pathomthongtaweechai, Peter R. Steinhagen, Papasara Chantawichitwong, Wilasinee Satianrapapong, Pawin Pongkorpsakol
Noncoding RNAs (ncRNAs), RNA transcripts without the capacity to produce proteins, have recently emerged as regulators of epigenetics and gene expression.219,220 MicroRNAs (miRNAs) are small ncRNAs of approximately 22 nucleotides in length. Owing to their versatility, they can repress or activate messenger RNAs (mRNAs) to subsequently inhibit or stimulate translation,221,222 respectively. In addition to miRNAs, long noncoding RNAs (lncRNAs) are ncRNAs of at least 200 nucleotides in length. They are also involved in mRNA stability and post-transcriptional regulation, similarly to miRNAs.223,224 Intriguingly, the dysregulation of ncRNAs is associated with gut barrier disruption and inflammation, which are the pathophysiological features of several gastrointestinal diseases. Therefore, the functions and applications of these ncRNAs have received growing attention in research on such diseases.225–228
A comprehensive update of siRNA delivery design strategies for targeted and effective gene silencing in gene therapy and other applications
Published in Expert Opinion on Drug Discovery, 2023
Ahmed Khaled Abosalha, Waqar Ahmad, Jacqueline Boyajian, Paromita Islam, Merry Ghebretatios, Sabrina Schaly, Rahul Thareja, Karan Arora, Satya Prakash
Andrew Fire and Craig Mello were awarded the Nobel Prize in 2006 for their discovery of ‘RNA interference-gene silencing by a double-stranded RNA.’ This new theory represented an advanced technique of gene therapies to control numerous gene-associated diseases. The process of gene silencing describes the employment of a 21–25-nucleotide, double-stranded RNA molecule known as ‘siRNA’ to control the post-transcriptional regulation of the mRNA of the targeted gene. The siRNA duplex is composed of two strands: a sense strand (i.e. passenger) and an antisense strand (i.e. guide). The guide strand is complementary to the mRNA of the targeted gene so that this strand can easily recognize it [1,2]. Four siRNA therapies are present in the market after the approval of the FDA and regulatory agencies. Patisiran was approved in 2018 for the management of a rare genetic disorder termed ‘Hereditary Variant Transthyretin Amyloidosis’ [3]. Givosiran was authorized in 2019 for the treatment of acute hepatic porphyria [4]. In 2020, Lumasiran was the third accepted siRNA for controlling primary hyperoxaluria type 1 [5]. Recently, Inclisiran was approved for the treatment of hypercholesterolemia [6]. The delivery of these therapies was achieved by either encapsulating the siRNA into lipid nanocarriers such as liposomes (e.g. Patisiran) or through conjugation using N-acetylgalactosamine (e.g. Givosiran, Lumasiran, and Inclisiran) [7]. Currently, there are several other siRNA therapies at different phases of clinical trials including Vutrisiran, Nedosiran, Fitusiran, Cosdosiran, Tivanisiran, and Teprasiran.