LingVitae - The Design Polymer Technology

A Design Polymer is a DNA
molecule consisting of a pattern with two specific DNA sequences, e.g. on 10 base pair each, denoted “0” and “1”.

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Target DNA molecules
on 24 base pairs are converted into Design Polymers in a biochemical three step process.

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The conversion process
is performed on a lab-on-a-disk platform. The entire conversion procedure where 100 billion target DNA molecules of 24bp each are converted into 48 unit Design Polymers

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Flexibility in design
iare keyword of paramount importance as we intend to tailor make Design Polymer products for our partners' individual SMS platforms.

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A new paradigm for DNA analysis based upon single molecule sequencing (SMS) is on the horizon, and a wide repertoire of technologies and approaches are being pursued.

For instance, nanopores and nanopipettes are being used for the controlled translocation of individual DNA molecules through small apertures, polymerases are being used for the controlled incorporation of labeled nucleotides, exonucleases are being used for the controlled degradation of target DNA molecules and AFM cantilevers are being used for topographical analysis, and so on.

However, in order to succeed with the development of a SMS platform several fundamental challenges must be addressed, such as:

Resolution – the basepairs in biological DNA molecule are separated with a distance of 0,34 nm
The basic DNA code consist of four different states (A, C, G and T)
Biological DNA molecules tend to form secondary structures

In order to address the above challenges LingVitae is developing a product portfolio consisting of advanced DNA preparation tools that will be tailor made for SMS platforms developed by our partners. A key element of the product portfolio is the conversion of biological DNA molecules into synthetic DNA molecules; Design Polymers.

Physical Magnification
The units to discriminate in a biological DNA molecule are bases or base pairs with a size of 0,34 nm each. The units to discriminate in a Design Polymer are blocks of up to 25 bases or base pairs with a size of up to 10 nm each.

Maximalisation of Unit Differences
The difference between the units to discriminate in a biological DNA molecule are only represented by a few atoms on a purine or pyrimidine skeleton attached to an identical backbone structure. The difference between the units to discriminate in a Design Polymer can be very significant and will be tailor made to achieve maximum resolution power on the read-out platform in question.

Binary Code
There are 4 units to discriminate between in a biological DNA molecule and the read-out platform must thus be able to distinguish between 4 different levels or states. There are 2 units to discriminate between in a Design Polymer and the read-out platform must thus be able to distinguish between only 2 different levels or states or alternatively even easier use a very simple on-off approach

Removal of secondary structures
A biological DNA molecule can take all forms of sequences and shapes and has a natural tendency to form secondary structures which can influence on the read-out process. A Design Polymer can be designed to avoid secondary structures and to ensure a reproducible behavior during the read-out process

Labels
It is difficult to label every individual base in biological DNA molecule due to sterical hindrance. The repertoire of labels that can be used is thus limited. Incorporation errors, quenching of neighbor labels, etc. adds to the challenge. It is easy to label every individual unit in Design Polymer as the spacing between labels, unit sequence, and more can be designed. The repertoire of labels that can be used are thus almost endless. Incorporation errors, quenching of neighbor labels, and other challenges can easily be solved by smart design of unit sequences, spacing, and other Design Polymer parameters.