DNA as an Antimicrobial Agent for Preventing Neisseria Gonorrhoeae Infection

This invention encompasses a series of DNA-based antimicrobial compounds that prevent transmission of Neisseria gonorrhoeae (Ngo) during sexual intercourse and possibly treat an extant Ngo infection, alone or in combination with antibiotics, while leaving commensals unharmed. These DNA molecules are effective against low-passage antibiotic sensitive and resistant Ngo clinical isolates through a unique and experimentally proven mode of action. 

These “killer” DNA molecules have the following attributes: They have defined nucleotide sequences with homology to genes essential for Ngo viability, linked to a DNA Uptake Sequence (DUS) that allows them to enter Ngo cells; and they are methylated differently than Ngo DNA. Upon entering Ngo, the “killer” DNAs attempt to recombine with homologous sequences in the chromosome; restriction/methylation systems in the cell recognize the DNA heteroduplexes as foreign because of their mismatched methylation signatures and nick these complexes, leading to chromosome instability and ultimately cell death. These DNA molecules kill over 90% of input Ngo cells in both buffered media and commercially available personal lubricants. These first-in-class microbicides are designed to be incorporated into personal lubricants that can be applied topically by the user prior to sexual intercourse, or into lubricants on condoms.  

Background: 
Gonorrhea is the second most reported bacterial sexually transmitted infection (STI). Each year, Neisseria gonorrhoeae (Ngo) causes over 1.5 million new infections in the United States, and >87 million worldwide. The decades-long effort to develop a gonorrhea vaccine has been unsuccessful, and the ability of Ngo to rapidly develop antibiotic resistance greatly limits the effectiveness of antibiotics currently approved for treating gonorrhea. The effectiveness of the few antibiotics in the development pipeline will be short-lived: Ngo has already developed resistance to Zoliflodacin, an antibiotic in Phase 3 clinical trials. Prevention and treatment of gonorrhea remain elusive goals. This invention addresses these needs. These DNA-based antimicrobial compounds, introduced topically in gel form to the genital surfaces during sexual intercourse, kill Ngo thereby preventing transmission. They do not harm commensals. Because these DNAs are delivered via personal lubricants, they will require less time for FDA approval than ingested and injected compounds.

Applications: 

• Topical treatment for preventing transmission of Neisseria gonorrhoeae during sexual intercourse
• Potential for treating extant Neisseria gonorrhoeae infections, alone or in combination with an antibiotic

Advantages: 

• Practical and convenient topical application by the user before sexual intercourse
• Purchased privately by user over-the-counter, avoiding social stigma associated with STIs
• Effective against drug resistant Ngo
• Certain DNA molecules convert ciprofloxacin resistant Ngo to antibiotic sensitivity
• Do not harm commensals
• Topical method of delivery involves fewer steps for FDA approval