By Ben Butkus
BioHelix has received a $300,000 Phase I Small Business Innovation Research grant from the National Institute of Allergy and Infectious Diseases to support the development of a low-cost, rapid, quantitative test for HIV-1, according to recently published grant information.
Under the grant, BioHelix will explore the use of zip nucleic acid, or ZNA, technology to enhance the speed and sensitivity of its isothermal amplification method, called helicase-dependent amplification, or HDA.
More specifically, BioHelix will compare the enhancement capabilities of the ZNA technology with that of several other nucleic acid probe technologies in order to identify the best one to help it commercialize a quantitative HIV-1 assay under the brand name IsoAmp.
Beverly, Mass.-based BioHelix has been exploring multiple routes to commercialize molecular diagnostic assays based on its HDA technology, which it claims is superior to PCR in the areas of cost, speed, specificity, and overcoming amplification inhibitors.
In October, the company received US Food and Drug Administration approval for its first assay based on the technology — the IsoAmp HSV test for detecting herpes simplex virus in genital and oral lesion specimens from symptomatic patients (PCR Insider, 10/20/2011).
BioHelix has also been developing IsoAmp molecular tests for infectious diseases such as chlamydia, gonorrhea, and tuberculosis; and has a partnership and licensing agreement with Quidel to develop molecular tests for several infectious diseases for use on Quidel's point-of-care device, still under development (PCR Insider, 4/14/2011).
Great Basin is also incorporating the technology in its cartridge-based, sample-to-answer molecular testing platform (PCR Insider, 2/17/2011); and, in the meantime, BioHelix has been working with researchers at Boston University under another NIAID grant to develop its own fully integrated point-of-care molecular diagnostic device that would combine HDA and lateral flow detection technology (PCR Insider, 10/13/12).
The most recent NIAID grant, awarded last month, will ultimately support a collaboration between BioHelix and the laboratory of Jeanne Jordan at George Washington University to develop a quantitative HIV RNA assay based on HDA and a portable, real-time fluorescence analyzer, primarily for use in near-patient or resource-limited settings.
However, in the initial phase of the grant, BioHelix will first attempt to enhance the performance of its HAD-based HIV assays with the ZNA or other possible oligonucleotide probe technologies.
Owned by French biotech firm Polyplus-transfection, but licensed to Sigma-Aldrich, ZNAs are oligonucleotides conjugated to a number of cationic spermine moieties that enhance the effective concentration of primers and probes near nucleic acid targets.
This property has been reported to enhance the speed and sensitivity of reverse transcriptase PCR, and the probes are compatible with Taqman detection formats, BioHelix said. As such, the company expects that the ZNA technology will increase the accuracy of its isothermal assays.
"We haven’t licensed the ZNA technology," BioHelix President and CEO Huimin Kong told PCR Insider in an e-mail this week. "This is a phase I award and we are doing feasibility research. If we demonstrate that it is feasible to use ZNAs, we may contact [Polyplus-transfection] to discuss a potential licensing agreement down the road."
Specifically, BioHelix and partners plan to compare the performance of the ZNA probes to that of locked nucleic acid, DNA dual-labeled, and cycling probe technologies; then test the sensitivity and specificity of assays using the ZNA technology in combination with IsoAmp in a panel of HIV-1 isolates.
The researchers in parallel will develop a "simple work flow for extraction of RNA from dry blood spots and dry plasma spots."
At the conclusion of Phase I, BioHelix "will be ready to identify the best probe technology to develop a commercial IsoAmp HIV-1 quantitative assay for commercial distribution in the US and abroad. We will also have a clear indication of the type of sample extraction method that best suits HDA viral load testing," the company wrote in its grant abstract.
In Phase II, BioHelix said that it would explore obtaining a pre-investigational device exemption for a multi-site clinical study with the hopes of seeking FDA approval of the test; and would also explore commercial release in the rest of the world.
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