LingVitae’s ‘genetic binary code’

Overview: Norwegian start-up LingVitae is developing a tool to translate biological data of interest into a form that can be more readily detected. It’s using a restriction and ligation enzyme system to cleave two end bases at a time from target DNA fragments of around 4- 40 bases[1], and effectively replace such two base combinations with predetermined, longer sequences of DNA (or DNA bound to labels), which are then concatenated into a new and much longer DNA strand. The process can be thought of as making a genetic binary code, where A, T, G, and C are replaced with, for example, 0-0, 0-1, 1-0, and 1-1 (where 0’s and 1’s correspond to distinct 10-base-long units). The resulting DNA concatemers would be amenable to hybridization with probe oligonucleotides[2]. In addition, a similar overall method could be used to convert protein sequences into nucleic acid sequences for detection[3].

Analysis: LingVitae’s technology is innovative and will no doubt find uses, though its applicability to third and fourth generation sequencing will be contingent on the success or failure of companies like Pacific Biosciences. Specifically, if third and fourth generation systems achieve a sufficient level of accuracy for single molecule detection by analyzing target molecules in their native state, then LingVitae’s technology will be less useful. LingVitae is also up against technical hurdles relating to the accuracy of its ligation-enzyme recognition and synthesis system. Furthermore, overall processing time (on the order of 24 hours for an entire eukaryotic genome[4]) is a downside which could severely limit use for whole genome sequencing. For genome sequencing, LingVitae’s technology appears to be a fit with platforms that are very high throughput but face detection accuracy problems. Thus, certain forms of nanopore sequencing would be a possible fit, given that detection methods such as ion current blockade are inadequate to resolve the identity of a single base within a DNA segment. The technology could therefore be a fit for Illumina (ILMN).

Copyright © Bruce A. Schiamberg 2010. All rights reserved.

References:

[1] Blow, Nature Methods, vol. 5, p. 267 (2008)

[2] US20070254280

[3] US20090047744

[4] Company website: http://www.lingvitae.com/

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