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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...

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DNAzyme 10-23 - Based Nanomachines for Nucleic Acid Recognition

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Published on: February 9, 2024

Universal translators for nucleic acid diagnosis.

John M Picuri¹, Brian M Frezza, M Reza Ghadiri

¹Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

Journal of the American Chemical Society

|July 2, 2009

Summary

Researchers developed universal molecular translators for rapid, accurate nucleic acid diagnostics. This innovation enables adapting a single assay for detecting multiple diseases, including HIV, hepatitis C, and avian influenza, without re-engineering the assay itself.

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Published on: November 5, 2019

Area of Science:

Biotechnology
Molecular Biology
Diagnostics

Background:

Current nucleic acid diagnostic assays are sequence-specific, requiring individual development and optimization for each new target.
This limits the adaptability and throughput of gene diagnostics, despite their growing biomedical importance.

Purpose of the Study:

To investigate PCR-independent isothermal molecular translation strategies for universal nucleic acid detection.
To demonstrate the adaptability of these translators for high-throughput disease diagnostics.
To explore translating small-molecule interactions into nucleic acid outputs.

Main Methods:

Development of PCR-independent isothermal molecular translation strategies.
Implementation using commercially available components without post-translation purification.
Application to adapt existing diagnostic systems for new targets (Hepatitis C, H5N1, smallpox).
Demonstration of aptamer-based translation of small molecules (adenosine) into DNA outputs.

Main Results:

Achieved translation yields up to 96% in 5 minutes at room temperature.
Demonstrated minimal background reactions (<1%) and discrimination of single nucleotide polymorphisms.
Successfully adapted a diagnostic system for high-throughput detection of Hepatitis C, avian influenza (H5N1), and smallpox.
Showcased translation of adenosine into a detectable DNA sequence using a DNA aptamer.

Conclusions:

Developed efficient and rapid molecular translation strategies for nucleic acid diagnostics.
Demonstrated the versatility of these translators for adapting assays to new disease targets.
Established the feasibility of translating small-molecule recognition events into nucleic acid signals for label-free detection.