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DNA oligonucleotides that can perform a specific chemical reaction
Deoxyribozymes, also called DNA enzymes, DNAzymes, or catalytic DNA, are DNA oligonucleotides that are capable of performing a specific chemical reaction, often but not always catalytic. This is similar to the action of other biological enzymes, such as proteins or ribozymes (enzymes composed of RNA). However, in contrast to the abundance of protein enzymes in biological systems and the discovery of biological ribozymes in the 1980s,
there is only little evidence for naturally occurring deoxyribozymes. Deoxyribozymes should not be confused with DNA aptamers which are oligonucleotides that selectively bind a target ligand, but do not catalyze a subsequent chemical reaction. With the exception of ribozymes, nucleic acid molecules within cells primarily serve as storage of genetic information due to its ability to form complementary base pairs, which allows for high fidelity copying and transfer of genetic information. In contrast, nucleic acid molecules are more limited in their catalytic ability, in comparison to protein enzymes, to just three types of interactions: hydrogen bonding, pi stacking, and metal ion coordination. This is due to the limited number of functional groups of the nucleic acid monomers: while proteins are built from up to twenty different amino acids with various functional groups, nucleic acids are built from just four chemically similar nucleobases. In addition, DNA lacks the 2' hydroxyl group found in RNA which limits the catalytic competency of deoxyribozymes even in comparison to ribozymes. In addition to the inherent inferiority of DNA catalytic activity, the apparent lack of naturally occurring deoxyribozymes may also be due to the primarily double stranded conformation of DNA in biological systems which would limit its physical flexibility and ability to form tertiary structures, and so would drastically limit the ability of double stranded DNA to act as a catalyst;

Of particular interest are DNA ligases. and DNA cleavage.

Because there are no known naturally occurring deoxyribozymes, most known deoxyribozyme sequences have been discovered through a high throughput in vitro selection technique, similar to SELEX. in vitro selection utilizes a "pool" of a large number of random DNA sequences (typically 1014–1015 unique strands) that can be screened for a specific catalytic activity. The pool is synthesized through solid phase synthesis such that each strand has two constant regions (primer binding sites for PCR amplification) flanking a random region of a certain length, typically 25–50 bases long. Thus the total number of unique strands, called the sequence space, is 4N where N denotes the number of bases in the random region. Because 425 ≈ 1015, there is no practical reason to choose random regions of less than 25 bases in length, while going above this number of bases means that the total sequence space cannot be surveyed. However, since there are likely many potential candidates for a given catalytic reaction within the sequence space, random regions of 50 and even higher have successfully yielded catalytic deoxyribozymes. which shows how oligonucleotides undergo competitive binding with the targets and how the evolutionary outcome can be improved through fine tuning of parameters. Deoxyribozymes obtained through in vitro selection will be optimized for the conditions during the selection, such as salt concentration, pH, and the presence of cofactors. Because of this, catalytic activity only in the presence of specific cofactors or other conditions can be achieved using positive selection steps, as well as negative selection steps against other undesired conditions.

A similar method of obtaining new deoxyribozymes is through in vitro evolution. Though this term is often used interchangeably with in vitro selection, in vitro evolution more appropriately refers to a slightly different procedure in which the initial oligonucleotide pool is genetically altered over subsequent rounds through genetic recombination or through point mutations. This first successful evolution of catalytic DNA from a non catalytic precursor could provide support for the RNA World hypothesis. In another recent study, an RNA ligase ribozyme was converted into a deoxyribozyme through in vitro evolution of the inactive deoxyribo analog of the ribozyme. The new RNA ligase deoxyribozyme contained just twelve point mutations, two of which had no effect on activity, and had a catalytic efficiency of approximately 1/10 of the original ribozyme, though the researches hypothesized that the activity could be further increased through further selection. This first evidence for transfer of function between different nucleic acids could provide support for various pre RNA World hypotheses.

Because most deoxyribozymes suffer from product inhibition and thus exhibit single turnover behavior, it is sometimes argued that deoxyribozymes do not exhibit "true" catalytic behavior since they cannot undergo multiple turnover catalysis like most biological enzymes. However, the general definition of a catalyst requires only that the substance speeds up the rate of a chemical reaction without being consumed by the reaction (i. e. it is not permanently chemically altered and can be recycled). Thus, by this definition, single turnover deoxyribozymes are indeed catalysts. Several studies have shown the usage of DNAzymes to inhibit influenza A and B virus replication in host cells. DNAzymes have also been shown to inhibit the replication of SARS coronavirus (SARS CoV), and HCV

Asthma is characterized by eosinophil induced inflammation motivated by a type 2 helper T cell (Th2). By targeting the transcription factor, GATA3, of the Th2 pathway, with DNAzyme it may be possible to negate the inflammation. The safety and efficacy of SB010, a novel 10 23 DNAzyme was evaluated, and found to have the ability to cleave and inactivate GATA3 messenger RNA in phase IIa clinical trials. Treatment with SB010 significantly offset both late and early asthmatic responses after allergen aggravation in male patients with allergic asthma. The transcription factor GATA 3 is also an interesting target, of the DNAzyme topical formulation SB012, for a novel therapeutic strategy in ulcerative colitis (UC). UC is an idiopathic inflammatory bowel diseases defined by chronically relapsing inflammations of the gastrointestinal tract, and characterized by a superficial, continuous mucosal inflammation, which predominantly affects the large intestine. Patients that do not effectively respond to current UC treatment strategies exhibit serious drawbacks one of which may lead to colorectal surgery, and can result in a severely compromised quality of life. Thus, patients with moderate or severe UC may significantly benefit from these new therapeutic alternatives, of which SB012 is in phase I clinical trials. Atopic dermatitis (AD) is a chronic inflammatory skin disorder, in which patients suffer from eczema, often severe pruritus on the affected skin, as well as complications and secondary infections. AD surfaces from an upregulation of Th2 modified immune responses, therefore a novel AD approach using DNAzymes targeting GATA 3 is a plausible treatment option. The topical DNAzyme SB011 is currently in phase II clinical trials. DNAzyme research for the treatment of cancer is also underway. The development of a 10 23 DNAzyme that can block the expression of IGF I (Insulin like growth factor I, a contributor to normal cell growth as well as tumorigenesis) by targeting its mRNA could be useful for blocking the secretion of IGF I from prostate storm primary cells ultimately inhibiting prostate tumor development. Additionally, with this treatment it is expected that hepatic metastasis would also be inhibited, via the inhibition of IGF I in the liver (the major source of serum IGF I). A DNAzyme based biosensor for lead ion was used to detect lead ion in water in St. Paul Public Schools in Minnesota. Furthermore, DNAzymes have been used in combination of aptamers and nucleic acid bioreceptors for the development of a multiplex bioassay.

Chirality is another property that a DNAzyme can exploit. DNA occurs in nature as a right handed double helix and in asymmetric synthesis a chiral catalyst is a valuable tool in the synthesis of chiral molecules from an achiral source. In one application an artificial DNA catalyst was prepared by attaching a copper ion to it through a spacer. The copper DNA complex catalysed a Diels Alder reaction in water between cyclopentadiene and an aza chalcone. The reaction products (endo and exo) were found to be present in an enantiomeric excess of 50%. Later it was found that an enantiomeric excess of 99% could be induced, and that both the rate and the enantioselectivity were related to the DNA sequence.

The hemin/G Quadruplex DNAzyme consists of G Quadruplex forming DNA that can bind the co factor hemin (a. k. a. Fe(III)Protoporphyrin IX), forming a complex that can perform certain oxidation reaction in the presence of hydrogen peroxide. This DNAzyme can oxidize small molecules, such as dopamine and adenosine triphosphate, but can also be used for the modification of peptides and proteins by attaching small molecules.

Other uses of DNA in chemistry are in DNA templated synthesis, Enantioselective catalysis, DNA nanowires and DNA computing.