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Aptamers Case Study
“Aptamer-based technology is capable of detecting threats in minutes, and can save lives on the battlefield and in urban or commercial applications.”
Rapid, effective and verifiable biological warfare agent (BWA) detection under field conditions is an important Department of Defense and Homeland Security issue. Conventional technology uses antibodies and complicated bio assays. Aptamers are short nucleic acid sequencescapable of binding a target with affinities comparable to antibodies. They can be produced by chemical synthesis and production is rapid, reproducible and inexpensive. They are insensitive to storage conditions and undergo reversible denaturation. Aptamers can be made to target body constituents, toxins, chemicals, cells, spores, and low or non-immunogenic substances.Antibodies are large molecules made to target highly immunogenic substances. Their production is expensive and time consuming and effectiveness may vary from batch to batch. They are sensitive to storage conditions and undergo irreversible denaturation. Because aptamers could be superior to antibodies for targeting or treating infectious agents, CMI was challenged by the US Air Force to produce biological agent detectors using aptamer-based technology.
Reaching the Solution
Aptamers were reported simultaneously in August 1990 by two separate research teams. From 1996 to 2011 CMI performed over 13 individual contracts under US Air Forcesponsorship to research and develop aptamer based detection and identification of BWAs and to produce a hand-held detection device. The CMI research team attacked this challenge by making aptamers to infectious agents that included Anthrax spores,Francisella tularensis, Venezuelan Equine Encephalitis, as well as Shiga toxin. Aptamers are traditionally selected using an in vitro method called SELEX (Systematic Evolution of Ligands by Exponential Enrichment). Noting the laborious nature of the SELEX process CMI researchers conceived and developed a more rapid selection process. Armed with aptamers that target BWAs, CMI and its partner Charles River Laboratories demonstrated a proof-of-concept system for the collection, detection and identification of potential bio warfare agents. Additional research illustrated that aptamers produced to Anthrax toxins have the potential for in-vivo anti-toxin therapy.
CMI’s research illustrated that aptamers can be made to a variety of possible organisms and compounds. CMI and USAF scientists were awarded two patents; an “Organic Semiconductor Recognition Complex and System”; and “Methods and Compositions for Aptamers against Anthrax”; and have one application currently under review by the US Patent office on “Methods and Compositions for a Process of Rapid Selection and Production of DNA Capture Elements” (see the list of CMI patents). This small, portable device is capable of collecting and identifying infectious agents within 10 minutes. It may be used on the battlefield or by first responders in situations demanding quick detection and identification of potentially harmful or deadly agents, such as anthrax. A cartridge in the device seals the sample and provides secure, verifiable chain of custody capability for confirmation of the field detection. This device can also be used as a single-step remote alert to known BWAs as well as unknown or new agents. CMI’s anti-toxin research also illustrated that specifically derived aptamers could protect cell culture against lethal Anthrax toxin challenge; and that Anthrax Protective Antigen aptamersproperly administered to mice protected them against a lethal dose (LD100) of intranasal Bacillus anthracis spores.
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