nucleic_acid

Nucleic acids are biopolymers, or large biomolecules, essential for all known forms of life. Nucleic acids, which include DNA (deoxyribonucleic acid) and RNA (ribonucleic acid), are made from monomers known as nucleotides. Each nucleotide has three components: a 5-carbon sugar, a phosphate group, and a nitrogenous base. If the sugar is deoxyribose, the polymer is DNA. If the sugar is ribose, the polymer is RNA. When sugar and a nitrogenous base get combined they form a nucleotide. Nucleotides are also known as phosphate nucleotides.

Nucleic acids are among the most important biological macromolecules (others being amino acids/proteins, sugars/carbohydrates, and lipids/fats). They are also found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information—in other words, information is conveyed through the nucleic acid sequence, or the order of nucleotides within a DNA or RNA molecule. Strings of nucleotides strung together in a specific sequence are the mechanism for storing and transmitting hereditary, or genetic information via protein synthesis.

Nucleic acids were discovered by Friedrich Miescher in 1869.

Experimental studies of nucleic acids constitute a major part of modern biological and medical research, and form a foundation for genome and forensic science, as well as the biotechnology and pharmaceutical industries.


Extracellular vesicles secreted by human glioma cells contain a wealth of tumor-specific proteins and nucleic acids that can be isolated from patients with these neoplasms. Thus, EV contribute to the development of biomarkers, and additionally have certain therapeutic potential for possible use in neurooncology and neurosurgery 1).


Nucleic acid-based therapy is a promising strategy to deliver bioactive molecules capable of promoting Axon regeneration. Branched polyethylenimine (bPEI: 25kDa) is one of the most widely studied nonviral vectors, but its clinical application has been limited due to its cytotoxicity and low transfection efficiency in the presence of serum proteins.

In a study, Gwak et al., synthesized cationic amphiphilic copolymers, poly (lactide-co-glycolide)-graft-polyethylenimine (PgP), by grafting low molecular weight PLGA (4kDa) to bPEI (25kDa) at approximately a 3:1 ratio as an efficient nonviral vector. We show that PgP micelle is capable of efficiently transfecting plasmid DNA (pDNA) and siRNA in the presence of 10% serum in neuroglioma (C6) cells, neuroblastoma (B35) cells, and primary E8 chick forebrain neurons (CFN) with pDNA transfection efficiencies of 58.8%, 75.1%, and 8.1%, respectively. We also show that PgP provides high-level transgene expression in the rat spinal cord in vivo that is substantially greater than that attained with bPEI. The combination of improved transfection and reduced cytotoxicity in vitro in the presence of serum and in vivo transfection of neural cells relative to conventional bPEI suggests that PgP may be a promising nonviral vector for therapeutic nucleic acid delivery for neural regeneration.

Gene therapy is a promising strategy to overcome barriers to Axon regeneration in the injured central nervous system. Branched polyethylenimine (bPEI: 25kDa) is one of the most widely studied nonviral vectors, but its clinical application has been limited due to cytotoxicity and low transfection efficiency in the presence of serum proteins. Here, we report cationic amphiphilic copolymers, poly (lactide-co-glycolide)-graft-polyethylenimine (PgP) that are capable of efficiently transfecting reporter genes and siRNA both in the presence of 10% serum in vitro and in the rat spinal cord in vivo. The combination of improved transfection and reduced cytotoxicity in the presence of serum as well as transfection of neural cells in vivo suggests PgP may be a promising nucleic acid carrier for CNS gene delivery 2).


1)
Santiago-Dieppa DR, Gonda DD, Cheung VJ, Steinberg JA, Carter BS, Chen CC. Extracellular Vesicles as a Platform for Glioma Therapeutic Development. Prog Neurol Surg. 2018;32:172-179. doi: 10.1159/000469689. Epub 2018 Jul 10. PubMed PMID: 29990983.
2)
Gwak SJ, Nice J, Zhang J, Green B, Macks C, Bae S, Webb K, Lee JS. Cationic, amphiphilic copolymer micelles as nucleic acid carriers for enhanced transfection in rat spinal cord. Acta Biomater. 2016 Apr 15;35:98-108. doi: 10.1016/j.actbio.2016.02.013. PubMed PMID: 26873365; PubMed Central PMCID: PMC4829463.
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