Meeting Summaries

Drug Delivery Workshop

In-Q-Tel, Inc.

Background – This workshop was motivated by BNext’s interest in technologies that facilitate timely response to infectious disease outbreaks through the rapid design and manufacture of vaccines against newly emergent pathogens. A compelling technology for rapid response to an ongoing outbreak is nucleic acid-based vaccines. Nucleic acid-based vaccines are attractive for rapid response because, in theory, DNA or RNA antigens that provoke a protective immune response could be quickly and inexpensively designed, manufactured, and used speedily in the clinic. Big pharma and biotech companies are interested in advancing nucleic acid-based vaccines. Several candidates are in clinical trials, though no nucleic acid-based vaccines have achieved FDA approval. Among the hurdles associated with DNA or RNA based vaccines are the following:

All Available Cellular Delivery Technologies Have Limitations – Major techniques to deliver the nucleic acid “payload” inside cells have been demonstrated – including electroporation, viral vectors and a variety of lipid nanocarriers – but all are problematic. Electroporation is suitable only for laboratory settings and not feasible in a mass casualty setting. Viral vectors carry the risk of unintentional immune reactions, and the virus carrier can only deliver certain types of payloads. Lipid nanocarriers are arguably the most advanced modality and are the delivery vehicle used in seven of eight ongoing RNA vaccine trials and in gene therapy trials. But they too are disadvantaged by the relatively “fragile” supply chain that is being used primarily for other products.

Manufacturing viruses and lipids is itself a hurdle to be overcome, especially if vaccine were needed in large quantities. For example, the supply chain capacity for GMP-grade lipids is limited, and currently being stretched by demand for the second-generation Shingles vaccine.

Similarly, manufacture of GMP-grade nucleic acid at scale is not currently possible at speed and would probably require 12 months. Making DNA in the U.S. Government’s Advanced Development Manufacturing Facilities may make this possible in 6 months. Several biotech companies are working hard to improve de novo DNA synthesis, but we are not yet able to do this at the required scale and time frame. DARPA is starting a program to develop novel approaches for DNA manufacturing at scale too.

Regulatory approval of novel cellular delivery methods requires a time-consuming and costly investment of resources, a fact that creates a rational disincentive to innovate. Nonetheless, successful and safe cellular delivery is a central feature of many of the most promising new drugs, including gene therapies. The commercial stakes involved in these new approaches will likely advance the science of cellular delivery, hopefully to the benefit of nucleic acid-based vaccines.

Conclusions: Advances in delivery modalities other than the current mainstays – existing viral vectors, lipid nanocarriers – should be supported. Supporting alternative DNA synthesis technologies and nimble, efficient biomanufacturing capabilities should be a priority.

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Data and Analytics, Meeting Summaries

Understanding Artificial Intelligence Applications in Bioscience and Biotechnology

In-Q-Tel, Inc.

Background – This paper reports on a November 15, 2018 Roundtable that explored opportunities and obstacles associated with applications of machine learning, deep learning, neural networks and other forms of “artificial intelligence” to bioscience, biotechnology and their application to biomedicine. The Roundtable was convened by IQT Labs, the research venture of In-Q-Tel (IQT), in collaboration with Lawrence Livermore National Laboratory (LLNL). Roundtable participants included multidisciplinary experts from industry, academia, finance and several U.S. government agencies. The discussion took place over a single day, included invited presentations from three participants, and was held on a not-for-attribution basis.

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Data and Analytics, Detection and Diagnostics, Meeting Summaries

Capabilities and Problems Associated with Detecting Engineered Microorganisms & Deducing Function

In-Q-Tel, Inc.

Background – This paper reports on a September 15, 2016 Roundtable Discussion convened by B.Next, an IQT Lab. The purpose of the discussion was to explore whether and how a biological sample containing microorganisms could be examined using current techniques and procedures to answer two questions:

  1. Is the sample likely to have been subject to genetic manipulation?
  2. If the sample was engineered, is it possible to determine the intended and actual functionality of the genetic manipulation?

It was assumed that national security imperatives would impose some urgency on the need for information, so that the time required for different approaches is of concern. It was also recognized that the sample material available for examination might be limited and possibly irreplaceable. The source and type of biological sample at issue was not defined. Both clinical samples (presumably collected in the wake of an attack) and other types of collected samples, including complex, “metagenomic” samples (e.g. environmental effluents) were considered.

The Roundtable included twenty-six participants, including scientists from academia, seven US Government agencies and the Lawrence Livermore National Lab, representatives from private sector companies engaged in DNA sequencing and bioinformatics, and IQT professional staff. The group’s expertise included bioinformatics, genetic engineering, computer science, microbiology, and biotechnology. The discussion took place over a single day, included invited presentations from three participants, and was held on a not-for-attribution basis.

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Detection and Diagnostics, Meeting Summaries, Technology and Market

Portable Sequencing for Infectious Disease Detection, Diagnosis, Discrimination, & Discovery

In-Q-Tel, Inc.

Background – This paper reports on a February 28, 2017 Roundtable Discussion convened by B.Next, an IQT Lab.

Several companies are developing DNA sequencing devices that can enable users to sequence DNA outside the traditional laboratory setting.  Among them, Oxford Nanopore is perhaps the most well-known.  The advent of portable sequencing devices opens up a wide variety of potential use cases that range from point-of-care medical diagnostics to on-site agricultural pest analysis.  It will soon be common for scientists to study animal and plant genetics and the structure of microbial communities close to where these species are found in nature.  In the realm of managing epidemics, the current state of portable sequencing technology presents potential opportunities to accelerate the collection of pathogen genomic sequence data during an outbreak.  Distributed sufficiently broadly, portable sequencers could function as “sensors” that help detect the spread and evolution of a pathogen.

The Roundtable included experts from industry, academia, finance and several USG agencies who manufacture, consume, invest in, or develop use cases for sequencing applications as they relate to disease outbreaks.  The discussion took place over a single day, included invited presentations from four participants plus prepared remarks from three others (see below), and was held on a not-for-attribution basis. (The participants agreed to allow IQT to publish a summary of key insights from the meeting.  In addition, participants named below consented to allow us to use their names in this report.)

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