Technology

Introduction

The DESTINA technology is unique and distinguishable from all existing enzymatic based detection systems. Application opportunities for DESTINA reagent use in molecular diagnostic assays are in development across multiple detection platforms, including MALDI-ToF, magnetic nanobeads, membranes, and sophisticated photonic and sound wave sensing devices. The superior specificity to current detection methods, with opportunity to undertake PCR free, direct detection of nucleic acids provides breakthrough solutions at a lower costs.

In the presence of all four aldehyde modified nucleobases (i.e. adenine, thymine guanine and cytosine derivatives) the nucleic acid template stabilizes the iminium species with the correct hydrogen-bonding motif (obeying Watson-Crick base-pairing), amplifying it over the other possible iminium products. This is reflected in the final product distribution after reduction to the corresponding amine, and provides a highly accurate means of nucleic acid discrimination. A correct detection signal can ONLY be achieved if: a) The target nucleic acid sequence binds in perfect alignment to DGL probe; b) The correct SMART Nucleobase seats into the pocket formed by the duplex AND; c) The SMART Nucleobase is "locked-in" chemically. If mis-alignments betw

Art of Technology

DESTINA Genomics Ltd. (DGL) technology is based on combining its patented aldehyde modified SMART Nucleobases with unique peptide nucleic acid (PNA) capture probes that have been synthesised with a ‘blank’ position (DGL probes). DGL technology applies "dynamic chemistry" to DGL probes for the development of an entirely novel chemical, rather than enzymatic, method for nucleic acid testing.

This revolutionary approach is based on the hypothesis that Watson-Crick base pairing could be harnessed to template a dynamic reaction on a strand of DGL probe. DGL probes seek out the correct target sequences, detecting the presence of genetic mutations by creating a nucleobase-free position on the DGL probe (a so-called positionchemical pocket) situated opposite to a nucleotide under interrogation on a complementary target nucleic acid strand (Scheme, step 1). A reversible reaction, between an aldehyde-modified SMART Nucleobase (Scheme, step 2) and the free secondary amine at the chemical pocket will generate an iminium intermediate that can be reduced (chemical locked) and then analysed (Scheme, step 3).

een the target nucleic acid and DGL probe, or random attachments of the target nucleic acid to array/bead surfaces occur (a recurrent problem with enzyme based detection systems), DGL chemistry does not detect this, hence NO "false positives" can be recorded.

DESTINA’s Strengths

DESTINA Genomics Ltd. (DGL) technology can be used to identify any known target nucleic acid sequence, including insertion and deletion mutations, as well as non-mutated nucleic acid sequences. This gives the DGL technology a unique, powerful position versus current detection methods. A particular advantage is the DGL technology’s ability to directly detect small RNA’s, without the multiple steps required by the current methods.

DGL probes and SMART Nucleobases can successfully be used on the three major diagnostic platforms in use today - mass spectrometry, fluorescence and colourimetric systems as well as electrochemical detection system.

DGL can deliver high specificity, sensitivity and speed, at realistic price points, from inexpensive rapid tests to multi-probe, multiplex assays that can diagnose and predict for patient disease outcomes if no medical/clinical intervention is undertaken. The future of stratified and personalised medicine will be based on these three requirements, at a realistic cost.

Scientific Publications

1. DNA Analysis by Dynamic Chemistry - si
2. Dynamic chemistry for enzyme-free allele discrimination in genotyping by MALDI-TOF mass spectrometry - Analytical Methods, 2011, 3, 1656-1663.
3. Novel Biochip Platform for Nucleic Acid Analysis - Sensors, 2012, 12, 8100-8111.
4. Novel bead-based platform for direct detection of unlabelled nucleic acids through Single Nucleobase Labelling - Talanta, 2016, 161, 489-496
5. Polymerase-free measurement of microRNA-122 with single base specificity using single molecule arrays: Detection of drug-induced liver injury, PLOS One, 2017, doi: journal.pone.0179669
6. Identification of Trypanosomatids by detecting Single Nucleotide Fingerprints using DNA analysis by Dynamic Chemistry with MALDI-ToF, Talanta, 2018, 299-307
7. A PCR-free technology to detect and quantify microRNAs directly from human plasma , Analyst, 2018, 143, 5676-5682
8. Time-Gated Luminescence Acquisition for Biochemical Sensing: miRNA Detection: Methods and Applications, Book Chapter, Fluorescence in Industry, Springer Ser Fluoresc, DOI 10.1007/4243_2018_4
9. New Platform for the Direct Profiling of microRNAs in Biofluids, Anal. Chem., 2019, 91 (9), 5874–5880
10. A colorimetric strategy based on dynamic chemistry for direct detection of Trypanosomatid species, Scientific Reports, 2019, 9, Article number: 3696
11. miR-122 direct detection in human serum by time-gated fluorescence imaging, Chem. Commun., 2019, 55, 14958-14961
12. Smartphone-Based Diagnosis of Parasitic Infections With Colorimetric Assays in Centrifuge Tubes, IEEE Access, 2019, 7, 185677 - 185686 DOI:10.1109/ACCESS.2019.2961230
13. Direct detection of miR-122 in hepatotoxicity using dynamic chemical labelling overcomes stability and isomiR challenges, Analytical Chemistry, 2020, doi: 10.1021/acs.analchem.9b05449