China
Africa
Explore chapters and articles related to this topic
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Locked Nucleic Acids are synthetic third-generation backbone modified RNA analogues in which chemical modifications are made to the ribose sugar moiety of a RNA nucleotide. The chemical modification involves an extra bridge connecting the 2′-oxygen and 4′-carbon atoms of the ring (see Figure 5.95). This bridge “locks” the ribose in the 3′-endo (North) conformation which is often found in the A-form of nucleic acid duplexes. LNA nucleotides can be modified to contain either DNA or RNA bases depending on their use.
Precision medicine for colorectal cancer
Published in Debmalya Barh, Precision Medicine in Cancers and Non-Communicable Diseases, 2018
Candan Hızel, Şükrü Tüzmen, Arsalan Amirfallah, Gizem Çalıbaşı Koçal, Duygu Abbasoğlu, Haluk Onat, Yeşim Yıldırım, Yasemin Baskın
The MS status of CRC could also be predicted depending on miRNA expression profiles (Schepeler et al., 2008; Carvalho et al., 2017; Liu D et al., 2017; Strubberg and Madison, 2017). Spotted locked nucleic acid (LNA)–based oligonucleotide microarrays can be utilized to screen the expression profiles of miRNAs. Hence, miRNAs can also be presented as promising tools to classify colon cancers as either MSI or MSS (T Schepeler et al., 2008; Carvalho et al., 2017; Liu J et al., 2017; Strubberg and Madison, 2017). Mutations within the TP53 gene are the most common genetic/genomic aberrations in human cancers such as CRC. The GeneChip p53 assay is based on the recently designed oligonucleotide microarray technology (Takahashi et al., 2003).
Aptamers and Cancer Nanotechnology
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
Omid C. Farokhzad, Sangyong Jon, Robert Langer
Aptamers are highly stable and may tolerate a wide range of temperature, pH (~ 4–9), and organic solvents without loss of activity, but these molecules are susceptible to nuclease degradation and renal clearance in vivo. Therefore, their pharmacokinetic properties must be enhanced prior to in vivo applications. Several approaches have been adopted to optimize the properties of aptamers, such as: (1) capping their terminal ends; (2) substituting naturally occurring nucleotides with unnatural nucleotides that are poor substrates for nuclease degradation (i.e., 2′-F, 2′-OCH3, or 2′-NH2-modified nucleotides); (3) substituting naturally occurring nucleotides with hydrocarbon linkers; and (4) use of L-enantiomers of nucleotides to generate mirror image aptamers commonly referred to as spiegelmers.42–45 Aptamers can also be stabilized using locked nucleic acid modifications to reduce conformational flexibility,46 circularized, linked together in pairs, or clustered onto a substrate. Alternatively, a nuclease resistant aptamer may be selected de novo using a pool of oligonucleotides with 2′-F- or 2′-OCH3-modified nucleotides. By combining some of these strategies, an aptamer’s half-life can be prolonged from several minutes to many hours.35To prolong the rate of clearance of aptamers, their size may be increased by conjugation with polymers such as polyethylene glycol (PEG).47
Current progress of miRNA-derivative nucleotide drugs: modifications, delivery systems, applications
Published in Expert Opinion on Drug Delivery, 2022
Charles Asakiya, Liye Zhu, Jieyu Yuhan, Longjiao Zhu, Kunlun Huang, Wentao Xu
LNA is a nucleotide engineering where natural nucleotides carry ribose 2′-O and 4′-C-atoms connect via a methylene bridge. LNA modification results in a unique high affinity, increased metabolic stability, melting temperature, proper or even improved mismatch discrimination[36]. Additionally, this type yields a significant increase in melting temperature, enhancing miRNA inhibition. A clinical study has shown that miravirsen, miR-122, a locked nucleic acid-modified antisense oligonucleotide, showed a high binding affinity, stability, and increased nuclease resistance. Another locked-nucleic acid clinical nucleotide drug is the MRG110, which targets miR-92a. Notwithstanding the therapeutic potentials of LNA oligonucleotides, a study carried out by Zhang and his team using LNA-mediated-anti-miR-155 revealed the FAM-labeled anti-miR-155 were efficiently taken up by bone marrow (BM) cells, which remained stable in the mice for more than a week after a single intravenous injection[37].
miRNAs as attractive diagnostic and therapeutic targets for Familial Mediterranean Fever
Published in Modern Rheumatology, 2021
Hamza Malik Okuyan, Mehmet A. Begen
Although many studies investigating the potential therapeutic role of miRNAs in pathological conditions have been performed at the preclinical levels in recent years, a limited number of miRNAs entered into clinical trials, and none of them have yet reached clinical phase III [97]. Due to various challenges, such as identifying the best candidate miRNAs, stability, and delivery, miRNA-based drug development has been delayed [97]. The selection of promising candidate miRNAs is the first crucial point in the development of miRNA-based drugs. Current databases providing knowledge about miRNAs in human diseases will help researchers identify more ideal miRNAs to develop therapeutics [99]. The stability issue caused by nucleases in physiological conditions is one of the important challenges in developing miRNAs-based therapeutics [97]. Modifications that alter oligonucleotide structures chemically through locked nucleic acid (LNA) and methylation are commonly utilized in miRNA-based therapeutics to avoid RNA degradation issues and increase the stability of RNAs. Antigomirs have LNA chemical modifications containing a bridge between the 2´O group and the 4′ carbon atom, whereas miRNA mimics involve methylation in their structures for higher stability [97,100]. In addition to these modifications, several approaches such as Liposomes and Dendrimers have been developed to improving in vivo delivery. However, the delivery of these miRNAs to targeted tissues in physiological conditions is still a considerable challenge for miRNA-based drugs [97].
Strategic advancements and multimodal applications of biofilm therapy
Published in Expert Opinion on Biological Therapy, 2021
Different FISH techniques like Peptide Nucleic Acid (PNA-FISH) are applicable in clinical biofilms that increase the affinity toward DNA and RNA. Locked Nucleic Acid (LNA-FISH) is used in early stages that show high affinity toward DNA and RNA in addition to short hybridization time and more flexibility in probe design. FISH techniques improve the recognition of elements and determine the quantitative description of substance. The other varieties of FISH techniques include CARD-FISH, DOPE-FISH and Combinational Labeling and Spectral Imaging Fluorescence in-situ hybridization (CLASI-FISH) that shows variation with the improvement on detection element [24,33,34]. FISH in combination with other techniques like FISH/MAR, FISH Raman and FISH nanosims reduces the risk of cross-feeding [35]. They are useful in combination with stable isotopes like heavy water i.e. deuterium oxide; imaging is performed at sub-micron resolution with high spatial resolution with sensitivity. Disadvantages of FISH techniques include lack of sensitivity, less probe permeation and hybridization efficiency and restricted amount of different target organism determination at the same time.