By Erika L. Roberts, ELR Lab Services LLC
Aptamers are SELEX (systematic evolution of ligands by exponential enrichment)-derived DNA and RNA strands that can be selected against a broad range of targets such as proteins, cells, viruses, microorganisms, toxins, and chemical compounds. Aptamers have a very high affinity and specificity to their targets, and like antigen-antibody interaction, they can also be known as “chemical antibodies.” Aptamers offer advantages over antibodies, including lower immunogenicity and toxicity, better tissue penetration, lower production costs, very long shelf life (in the lyophilized form), and easier conjugation or modification. They are also popular as stand-alone binding reagents used in analytical chemistry analysis, which is the most common use of them today.
The production of conventional animal-based specific antibodies used for reagents and drug discovery is tedious, very expensive, and challenging. There are batch-to-batch variations with antibodies, which further limits their applications, and a much larger manufacturing facility is needed for their production and development. Antibodies also have a shorter shelf life than a lyophilized aptamer, which can last for decades at room temperature and offer much greater cost savings and stability. These benefits of various aptamers for selective, sensitive, and on-site target detection and for use as stand-alone therapies mean they have a very promising future.
Currently, there is an FDA approved aptamer therapy for macular degeneration (Macugen), which shows that there is a market and approval track already proven for therapies using aptamers.
So, with all the benefits of aptamers over traditional antibodies for possible targeted therapeutics, why have we not seen more of these come to market? With their cheaper cost to develop and manufacture, along with a decades-long shelf life in the lyophilized form, this would seem like the “holy grail” for reducing costs and providing more targeted therapies to larger and more remote markets of the world.
The current challenges in the market and why we have not seen more targeted therapies using aptamers can be attributed to two issues: lack of access to intellectual property and a shortage of personnel/facilities needed to manufacture and research aptamers. Let’s take a look at each of these issues and how the industry and academia are working to boost aptamer use.
Recent Patent Expiry Of SELEX Process Drives Innovation
For more than two decades, the development of aptamers was constrained by patent protection of the aptamer selection process known as SELEX. Since SELEX emerged in 1990, many selection methods have been developed for isolating aptamers. Importantly, monitoring enriching progress of candidate aptamers has always been the key and restrictive step in the SELEX process. To date, many different assay methods have been evaluated for monitoring and enriching aptamer libraries.
In my quest to understand the current state of the aptamer market and development since the patent expiration of SELEX, I talked to G. Thomas Caltagirone, Ph.D., president and CEO of Aptagen, a biotech developing aptamers for almost 20 years. Caltagirone notes that innovation for aptamer development and manufacturing was stifled due to the patent held for the SELEX process. It was only within the few years since the patent expiry (which was in October 2013) that aptamer innovation has accelerated and started to reach a much broader audience in the scientific community. In the long run, aptamers will be a definite competitor, if not a contemporary, to antibodies; however, since antibodies have been on the market for a much longer time than aptamers, there is still a “long way to go” (in Caltagirone’s words) to see them replace antibodies in targeted therapies, but it is most definitely a possibility.
With the recent expiration of SELEX patents and availability of key IP, aptamer innovation and uses are expected to increase over the next decade and beyond.
University Education Helps Turn The Tide
Difficulties in finding the right talent, and how that has limited how many projects and clients that aptamer developers can service at a time, means there is more work than lab scientists in the field. Currently, the backlog and shortage can be addressed by supporting companies that have a very robust internship program and are dedicated to training the next generation of lab scientists in the area of aptamer development and application. Since smaller companies have a harder time attracting talent than larger companies, there is also a good deal of competition from larger companies for talent with the specific background that is required — mainly molecular biologists and chemists. Just as in many businesses today, inside and outside the STEM fields, the shortage of qualified analysts is inhibiting innovation in aptamer development and applications.
Compared to 20 years ago, there is much more visibility of the life sciences field in the university system and many degrees are offered that can be specifically tailored to a career in the biotechnology field and, more specifically, aptamer development. When I graduated college (long ago), there were only a few avenues of employment or continuing education for an individual graduating with a molecular biology degree: 1) medical school, 2) dental/optometry school, 3) veterinary school, or 4) researcher in an academic setting. Over time, it has been encouraging to see the field of biotechnology emerge and add its legitimacy as a viable employment opportunity in the labor market. Consequently, universities and the business community have started to tailor their academic offerings to train the future molecular biologists and chemists that will be needed to support endeavors like aptamers.
For example, at The University of Texas at Austin, undergraduate students have used aptamer selection and development technologies in a teaching laboratory to build technical and 21st century skills appropriate for research scientists. Students develop and execute their own projects.
I am confident that the labor shortage is only a short-term issue, and as the field expands and has greater visibility, more and more future scientists and entrepreneurs will be drawn the field of aptamer development.
Aptamers have the potential to provide a safer, less toxic, more stable, and cheaper alternative to antibody therapies. Now that the SELEX patents have expired, innovation in the marketplace is picking up speed and we are seeing more research dedicated to using aptamers in the therapeutic and drug discovery market. This technology can deliver a cost advantage over many more expensive therapeutics and can also reach emerging markets where traditional antibody therapies are not viable due to storage and shipping challenges. In addition to their use in therapies, utilizing aptamers as biomarkers for disease and cancer detection can also open access to care in more rural areas by providing a stable and longer shelf-life reagent than what is currently the standard today. This can help provide more cost-effective and stable diagnosis and treatment of diseases in communities that would otherwise not have access. More research and development is needed to bring these amazing alternatives to antibodies to market, but we are well on our way.
About The Author:
Erika L. Roberts, MFS, is principal consultant and owner of ELR Lab Services LLC. Having more than 15 years of experience working in many different areas of the pharmaceutical/biotech manufacturing quality environments, she has particular expertise in sterility testing, microbial identification training, HPLC analysis, cGMP training, analytical chemistry, and pharmaceutical regulations. Roberts obtained a master’s in forensic science in 2006 with an emphasis in document examination.