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The Emerging Field of RNA Nanotechnology
Published in Lajos P. Balogh, Nano-Enabled Medical Applications, 2020
The most challenging aspect of RNA therapeutics is the yield and cost of RNA production. Commercial RNA chemical synthesis can only offer 40 (conservative) to 80 (with low yield) nucleotides. Acetalester 2′ -OH protecting groups, such as pivaloyloxymethyl, have been reported to enhance chemical synthesis of RNA. RNase ligase II has been shown to be a good alternative over the traditional T4 DNA ligase to generate longer RNA by ligation of two shorter synthetic RNA fragments [115]. In enzymatic synthesis, heterogeneity of the 3′ -end has been an issue [116]; this can be addressed by extending the transcribed sequence beyond the intended end and then cleaving the RNA at the desired site using ribozymes, DNAzymes, or RNase H [115–117]. Large scale RNA complexes produced in bacteria escorted by a tRNA vector have also been reported [40, 41]. Based on the rapid reduction of cost over the history of DNA synthesis, it is expected that the cost of RNA synthesis will gradually decrease with the development of industrial-scale RNA production technologies.
Basic Cell Biology
Published in Kedar N. Prasad, Handbook of RADIOBIOLOGY, 2020
Several enzymes are required for DNA synthesis. The enzymes thymidine kinase and DNA polymerase have been studied in relation to radiation damage in some detail. DNA is degraded by a specific enzyme referred to as DNAse (deoxyribonuclease).
A Brief History of Genetic Therapy: Gene Therapy, Antisense Technology, and Genomics
Published in Eric Wickstrom, Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors, 2020
Success in the modification of oligonucleotide backbone structure led to efforts to develop a host of new chemical formulations of oligonucleotides—efforts which continue today. These modifications range from different extents of backbone modification to complete redesign of intemucleotide linkages, sugar structure, sidechain chemistry and to oligonucleotides conjugated with other bioactive molecules (Hélène, 1989; Letsinger et al., 1989; Perbost et al., 1989; Rayner et al., 1989; Goodchild, 1990). In addition to new developments in DNA synthesis, techniques were also developed to perform automated RNA synthesis (Pfister et al., 1989).
Tumor microenvironment-responsive micelles assembled from a prodrug of mitoxantrone and 1-methyl tryptophan for enhanced chemo-immunotherapy
Published in Drug Delivery, 2023
Ru Wang, Nuannuan Li, Tianyu Zhang, Yiying Sun, Xiaoyan He, Xiaoyan Lu, Liuxiang Chu, Kaoxiang Sun
Chemotherapy is the main treatment method for breast cancer. The anthraquinone mitoxantrone (MX) (An et al., 2021) is efficacious against breast cancer. It can produce an anti-tumor effect by disturbing DNA synthesis (Evison et al., 2016; Granja et al., 2021). Some studies have shown that MX can also induce immunogenic-cell death (ICD) (Kepp et al., 2019). ICD can promote damage-associated molecular patterns (Zhou et al., 2019; Kim et al., 2022) in dying cancer cells, including exposure of calreticulin (CRT) (Mei et al., 2020) on the membrane surface, release of high mobility group box 1 (HMGB1), and secretion of adenosine triphosphate (ATP) (Li et al., 2020). All of these substances activate dendritic cells (Dudek et al., 2013) to devour dying tumor cells and recruit activated cytotoxic T cells to the tumor site. However, this process also induces overexpression of indole amine 2,3-dioxygenase (IDO) in tumor cells (Li et al., 2021) and activation of regulatory T cells (Tregs). These actions can further inhibit the functions of effector T cells and natural killer cells, thereby weakening the therapeutic effect of ICD (Li et al., 2021; Yang et al., 2022).
Levels of Folate and Vitamin B12, and Genetic Polymorphisms Involved in One-Carbon Metabolism May Increase the Risk of Cervical Cytological Abnormalities
Published in Nutrition and Cancer, 2022
Nayara Nascimento Toledo Silva, Ana Carolina Silva Santos, Maria de Fátima Dias de Sousa Brito, Diama Bradha Andrade Peixoto do Vale, Cláudia Martins Carneiro, Angélica Alves Lima
MTHFR C677T is the most studied among the polymorphisms that occur in folate metabolism in relation to cervical cancer. MTHFR enzyme may modify the susceptibility to carcinogenesis by modulating the availability of 5,10-methyleneTHF at different points in the folate metabolism. This coenzymatic form of folate plays a central role in one-carbon metabolism because 5,10-methyleneTHF can be directly transferred to dUMP in thymidylate synthesis, reduced to 5-methylTHF by MTHFR for methionine synthesis, or oxidized to 10-formylTHF for de novo synthesis of purines. Thus, the reduction of MTHFR enzymatic activity caused by C677T polymorphism may result in a lower synthesis rate of 5-methylTHF, which leads to an increase availability of 5,10-methyleneTHF for nucleotide production. It is essential for DNA synthesis and repair. On the other hand, a lower proportion of 5-methylTHF is available for the methylation pathway (24).
Strengths and caveats of identifying resistance genes from whole genome sequencing data
Published in Expert Review of Anti-infective Therapy, 2022
Brian M. Forde, David M. P. De Oliveira, Caitlin Falconer, Bianca Graves, Patrick N. A. Harris
A variety of platforms are currently available for microbial WGS. Selection of technology is often dependent on the objective of sequencing, surrounding factors encompassing genome coverage, time, high/low-throughput capacity, and expense [42]. Sequencing technologies can be divided into either short-read sequencing (Illumina, 454 pyrosequencing, and Ion Torrent) or long-read sequencing (Pacific Biosciences [PacBio] single molecule and Oxford Nanopore Technologies [ONT]) offering distinct advantages and disadvantages for the end-user (Table 1). The read-length is defined as part of the genome sequence that relates to a single length of DNA. Short read platforms such as Illumina are the most employed sequencing instruments for bacterial WGS, producing fragments <300 base pairs in size. For Illumina platforms, DNA fragments are synthesized from fluorescently labeled nucleotides. Fluorescently labeled nucleotides are added and detected during each step of DNA synthesis. Due to the high number of sequence reads, Illumina provides high-level data-output accuracy.