Fascinating chemistry based on the concept of 'avidity' for sequencing from Element Biosciences described in this recent @biorxivpreprint

It fundamentally differs from sequencing by synthesis (SBS) technology as used in NGS by Illumina, hence it tickled my fancy to write a 🧵:
https://www.biorxiv.org/content/10.1101/2022.11.03.514117v1

Sequencing by synthesis works by sequential incorporation (catalyzed by polymerase) and detection of synthetic nucleotides.
1/n

Practically needs micromolar amounts of enzyme + substrate ie nucleotides conjugated to fluorescent dye (detection) + blocking group (1 base at a time)

Avidity sequencing chemically decouples detection from polymerase extension allowing separate optimizations of each step. That helped reduce working concentration of the new reagents.

The idea of decoupling was also pursued by BGI using antibodies in 2020,
https://www.biorxiv.org/content/10.1101/2020.02.19.953307v1
2/n

Avidity in this context implies the cumulative strength of multiple base pair interactions as opposed to single base pair binding events that SBS relies on.

Stronger interaction means lower substrate concentration needed and longer residence time ➡️ enables imaging without bond formation

Some nice biochemical characterization summarized in the figure below from the paper to crunch kinetic rates from -
3/n