Firebird Diagnostics LLC

BIVER^TM

Home
Technology
BIVER^TM

Biversal Bases: BIVER^TM

Managing pathogen evolution

Problem

Pathogens are always evolving and, as they do, mutations in their genome can let them evade primers and probes used to detect them. This presents challenges for DNA- and RNA-targeted diagnostics in infectious diseases, but also in cancer, inherited diseases, and elsewhere in medicine.

Solution

Engineer nucleotide bases that pair with both the native and the most common replacement after mutation. The “binary” versatility lets one primer or probe detect the pathogen both before and after mutation.

Impact

Biversals are being developed to manage COVID-19 evolution, and as well as the evolution of HIV, mosquito-borne pathogens, and tick-borne pathogens. Future applications focus on the evolution of cancer genes in humans.

Chemistry behind BIVER^TM

With nucleotide bases, pairing rules are determined by the arrangement of hydrogen bond donor and receptor sites. In natural nucleotide bases, this arrangement is fixed. However, it is possible to create nucleotide basis where this arrangement is flexible, called biversals. With biversal nucleotide bases the arrangement of hydrogen bond donor and receptor sites is undetermined (i.e. it can switch between multiple stable forms) until it has paired with a natural base. This allows biversal bases to pair with more than one natural nucleotide.

Firebird has developed two biversal bases, one purine and the other pyrimidine. The purine biversal can pair with both C and T, while the pyrimidine can pair with both A and G.

Biversal bases can be incorporated into DNA and RNA and work with standard polymerases.

Publications

BIVER Purine

Purine biversal has two stable forms which allow pairing with C or T

BIVER Pyrimidine

Pyrimidine biversal has two stable forms which allow pairing with A or G