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Deoxyribozymes-Based Anti-monkeypox Drug Discovery Solutions
Introduction to Monkeypox Virus
Monkeypox virus (MPXV) is a virus belonging to the Poxviridae family, Chordopoxvirinae subfamily, the Orthopoxvirus genus. It was first isolated and identified in 1958 when monkeys shipped from Singapore to a Denmark research facility feel ill. However, the first confirmed human case was in 1970 when the virus was isolated from a child in the Democratic Republic of Congo suspected to have smallpox. Since the eradication of smallpox approximately 42 years ago, monkeypox virus remains the most pathogenic poxvirus and a major threat to global health security. On electron microscopy, the monkeypox virus is relatively large (200-250 nanometers). Poxviruses are brick-shaped, surrounded by a lipoprotein envelope with a linear double-stranded DNA genome. Aside from their reliance on host ribosomes for mRNA translation, poxviruses include all necessary replication, transcription, assembly, and egress proteins in their genome.
In 1994, a synthetic 35-bp polydeoxyribonucleotide was reported, being capable of catalyzing specific ribonucleotides or deoxyribonucleotides to form phosphodiester bonds, which was known as catalytically active DNA deoxyribozyme or DNase. In 1995, a DNA with ligase activity was reported, which catalyzed the formation of a phosphate bond between two DNA fragments complementary to it. Dozens of deoxyribozymes have been discovered in recent years. Deoxyribozymes 10~23 are the most promising ones. As a potentially powerful RNA-specific cleavage tool, deoxyribozymes 10~23 consist of 29 nucleotides with 15 nucleotides in the catalytic center. A seven-nucleotide binding arm is attached to each side of the catalytic center to bind the substrate RNA. The cleavage reaction occurs between the purine and pyrimidine of the RNA molecule. The 5' end product produced by the cleavage reaction has a 2'-3 'cyclic phosphate group, and the 3' end product contains free 5'-OH. Studies have shown that deoxyribozymes 10-23 act as synthetic substrates consistent with 15-17 single nucleotides in the initial regions of mRNA translation of HIV-1gag/pol, env, vpr, tat, and nef, which accurately and efficiently cleave the substrate mRNA molecules at the expected sites to inhibit the expression of these genes.
Fig.1 Cleavage of housekeeping gene mRNA can cause cancer cell death. (Daria D. 2020)
Deoxyribozymes-based Anti-Monkeypox Drug Discovery Solutions
Currently, there are no specific clinically proven treatments for monkeypox infection. Deoxyribozymes, which are able to bind and cleave complementary RNA sequences to inhibit protein expression, are potential therapeutic tools for MPX therapy development.
At Creative Biolabs, we provide services for the design and target screening of cleaved MPXV RNA deoxyribozyme, and verify the cleavage activity of deoxyribozyme on MPXV RNA at the extracellular molecular level. We also provide deoxyribozymes-based anti-Monkeypox drug development services to our clients all over the world.