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RainDance, BSRI Partner to Quantify Latent HIV at Newly Created AmfAR Research Institute

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This article has been updated from a previous version to correct the number of droplets generated by the RainDance digital PCR system.

NEW YORK (GenomeWeb) – With the goal of developing the scientific basis for an HIV cure by 2020, the American Foundation for Aids Research, or amfAR, will invest $20 million over five years into basic and clinical research at a network headquartered at the University of California, San Francisco.

To enable the overall research goals, the Blood Systems Research Institute and RainDance Technologies have in turn announced a collaboration to develop assays and protocols to measure latent HIV reservoirs.

Latent HIV is a critical stumbling block to viral eradication. Recent research suggests the virus may lie dormant, invisible to the immune system and traditional blood screening tests, in very specific tissue areas. A therapy called "shock and kill," which is the strategy being pursued by the San Francisco-based amfAR team, would provoke host immune cells to eject latent HIV into the blood stream, making it newly vulnerable to immunotherapies.

However, quantitation and detection of true latency requires sensitive technologies, and current methods are limited in their ability to detect a few target molecules in a high background.

The BSRI collaboration aims to develop "ultra-sensitive, highly precise, and low-cost [next-generation sequencing] and digital PCR methods to detect, measure, and monitor replication-competent latent HIV with absolute quantitation from limited amounts of bio-available fluids," RainDance noted in a statement today.

Specifically, the collaboration will use the company's RainDrop Digital PCR and ThunderBolts Next-Generation Sequencing platforms, which are commercially available as a unified system, Roopom Banerjee, president and CEO of RainDance, told GenomeWeb in an interview.  

"It's the only system out there that does both targeted next-generation sequencing as well as digital PCR," explained Banerjee.

This dual functionality may be particularly useful to latent HIV research, as well as to infectious disease or cancer research in general, where NGS can be used for screening and discovery of targets, mutations, and pathways. The digital PCR side of the system, which Banerjee noted is roughly 100 times more sensitive than NGS, can be used to track and monitor low-level mutations that are undetectable by most other means.

ThunderBolts is designed to be a lower-cost, lower-throughput system that can be used by any research lab, ranging from small-scale NGS validation studies on up to cancer centers researching liquid biopsy opportunities, said Banerjee.  

The firm also markets a platform called Thunderstorm, which is a "high-throughput, industrial-scale workhorse for targeted next-generation sequencing primarily in large core laboratories running between 2,000 to several hundred thousand samples per year," he said.

Banerjee said RainDance identified researchers at UCSF and BSRI through personal and sales connections, and began discussions in early 2014. At the JP Morgan Healthcare conference that year, Banerjee said the molecular pathology market represents a $1 billion opportunity, but that RainDance also intended to expand beyond that market and planned a future assay targeting latent HIV.

The firm has now been working with BSRI more intensively for about a year, and data from that work is expected to culminate in peer-reviewed publications soon, he said.

Digital PCR has been pursued by others as a tool to evaluate viral eradication. In theory, the high sensitivity of the method could allow researchers to confidently declare that there are no particles of virus remaining in a patient's sample.

As previously reported, the Droplet Digital PCR platform from Bio-Rad is being used for absolute HIV quantification, for example. A few studies have noted the presence of false-positive droplets using that system, with more recent work documenting improved sensitivity but also cases of negative control samples being scored as positive due to the presence of single presumably-false positive droplets.

The RainDance system partitions samples into some 10 million droplets, which is 500 times greater than the number generated by the Bio-Rad system, Banerjee said.

"That allows us to be true single molecule, and in that way eliminate false positives by higher compartmentalization and digitization of the sample," he said. Indeed, in a published study measuring the limit of detection for two assays of EGFR point mutations, the firm measured a false-positive rate of one in 14 million.

RainDance is a research-use only genomics tools supplier at this stage, Banerjee noted, but the firm is continuing to cultivate multiple collaborations in the HIV research space.

Besides BSRI and UCSF, the newly created amfAR Institute for HIV Cure Research also includes the Gladstone Institute of Virology and Immunology, Oregon Health and Science University, the University of California, Berkeley, Gilead Sciences, and the Infectious Disease Research Institute in Seattle.

Researchers will collaborate across the network with four main objectives: locating latent HIV reservoirs, determining how they are formed and persist, quantifying the amount of virus in these reservoirs, and, ultimately, eradicating them to cure HIV infection.

The BSRI team will be co-led by Satish Pillai, an associate investigator at BSRI and associate director the the UCSF-Gladstone Center for AIDS Research, and Michael Busch, senior vice president of research and director at BSRI and a professor of laboratory medicine at UCSF.

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