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Bioweapons from XNA Dre'Mont Jones Broncos Jersey , a Nuclease Resistant Synthetic Genetic Polymer that can Supplant DNA Health Articles | November 13, 2017



Containment and safety issues pertaining to synthetic biology has led to the synthesis of artificial nucleotides that can form synthetic genetic polymers known as Xeno nucleic acids (XNA). Xeno nucleic acids are versatile molecules that can be used to store, transfer, and propagate genetic information; they can also be used as drugs, sensors, catalysts, and regulatory molecules. In this paper, I discuss both the positive and negative applications of xenotechnology; in particular, its potential use as bioweapons are discussed.


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INTRODUCTION


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The arrival of novel life forms via synthetic biology (biological engineering) brought about atypical problems: (1) uncertainty of behaviour and interaction of artificial life forms with existing life forms as well as the ecosystem as a whole, (2) safety concerns for humans Drew Lock Broncos Jersey , and (3) containment issues (Acevedo-Rocha & Budisa, 2016; Schmidt, 2010; Tucker & Zilinskas, 2006). In an attempt to address all such concerns, XNAs – xeno nucleic acids based information storage - were designed as an alternative to the genuine deoxyribose or ribose based nucleic acids that form DNA (Fiers et al., 2016; Marliere, 2009; RJ, 2015; Diafa & Hollenstein, 2015). Organisms with XNA content cannot grow in nature as artificial synthetic nutrients must be supplied for sustained activity (Herdewijn & Marliere, 2009). In XNAs Dalton Risner Broncos Jersey , alterations are made to the sugar of natural nucleobases by replacing it with another sugar or non-sugar moiety to form xeno nucleotides; alternatively, modifications can also be made to the nucleobase (C5 in pyrimidine or N7 in purine) or the backbone (Diafa & Hollenstein, 2015; Johnson, 2015). For instance, hexitol nucleic acid (HNA) contains a hexose instead of the traditional deoxyriboseribose. Modifications to the nucleobase can alter strength and specificity of binding whereas modifications to the backbone can greatly increase resistance to nucleases (Morihiro, Kasahara, & Obika, 2017). There are a multitude of xeno nucleic acids amongst which 1,5-anhydrohexitol nucleic acid (HNA), cyclohexene nucleic acid (CeNA) Noah Fant Broncos Jersey , threose nucleic acid (TNA), glycol nucleic acid (GNA), locked nucleic acid (LNA), peptide nucleic acid (PNA), homochiral DNA (hDNA), xylonucleic acid (XyNA), deoxy-xylonucleic acids (dXyNA), arabinonucleic acid (ANA), 2′- deoxy-2′-fluoroarabinonucleic acid (FANA), 2′-deoxy-2′-fluororibonucleic acid (FRNA). Threose nucleic acid (TNA) Royce Freeman Broncos Jersey , hexitol nucleic acid (HNA), and glycol nucleic acid (GNA) can form double helices (Schmidt, 2010). Much like DNA, XNA can be utilised to pack information that can be duplicated using mutated forms of naturally existing polymerases (Steele & Gold, 2012). Natural polymerases stringently exclude xeno nucleic acids. However, Steele and Gold (2012) isolated functional polymerases for xeno nucleic acids by placing xeno nucleotides, primers, and plasmids coding for the engineered polymerases. The formation of synthetic genetic polymers (XNA) using mutated polymerases are verified using primer extension assays. Screening and identification of engineered polymerases that can ligates more than a few xeno nucleic acids are then optimized via directed evolution and molecular tweaking (Chaput, Yu, & Zhang Courtland Sutton Broncos Jersey , 2012). Replication of XNA as well as synthesis of XNA from DNA as well as reverse transcription of DNA from XNA can be carried out using said engineered polymerases (V. B. Pinheiro et al., 2012); engineered polymerases are commercially available for αS, CyDNA, fDNA, RNA, 2’F, 2’Ome, 2’Seme, 2’N3, ANA Bradley Chubb Broncos Jersey , FANA, HNA, CeNA, TNA, and LNA (Vitor BPinheiro & Holliger, 2012). Bst DNA polymerase (in the presence of MgCl2+) has been shown to extend 60% of a TNA template into DNA (Dunn & Chaput, 2016). In fact, with reverse transcription from XNA to DNA, information can be decoded and proteins synthesized from designed synthetic genetic polymers. The various XNAs have specific binding patterns. XNAs can base pair with both DNA and RNA. (R)-GNA and hDNA, on the other hand Phillip Lindsay Broncos Jersey , do not pair with DNA or RNA, giving them a unique property – one that can enter natural cells without interfering; xylonucleic acid (XyNA) and deoxy-xylonucleic acids (dXyNA) can bind both RNA poly A strands and DNA at once leading to the formation of a triplex (Anosova et al., 2016). Synthetic xeno polymers can be utilised to store and propagate the genetic code, as drugs, sensors, catalysts, and to regulate gene expression. This paper outlines the positive and negative aspects of the synthetic system; I argue in this paper that the synthetic system can also be utilized as a bioweapon – to design drugs that are anywhere from mildly toxic to deadly.


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APPLICATIONS


Antisense XNA oligonucleotides (ASO)


Nucleic acids can themselves be utilised as a drug for remedying diseases; however, (1) degradation of unprotected molecules by nucleases, and (2) poor binding to target molecules as well as large dose requirements were previously an obstacle (Morihiro et al., 2017). Contrary to DNA Joe Flacco Broncos Jersey , XNA is nuclease resistant and as such can parade through cellular machinery undetected, and unscathed. For instance, antisense oligonucleotides target mRNA and microRNA sequence (Morihiro et al., 2017). Binding of antisense oligonucleotide (ASO) to its target sequence initiates degradation; in fact, binding of antisense XNA oligonucleotide to its target blocks translation thereby modifying the protein content of the cellular system. Viruses such as HIV, influenza virus, herpes simplex virus, cytomegalovirus, Epstein Barr virus, hepatitis B virus and human papilloma virus are effective targets of ASOs (Bai Von Miller Broncos Jersey , You, Bo, &