CRISPR is Coming… Game of Clones

Where do popular television and science intersect? It’s not so far-fetched to ask where genetic innovation is taking us, and who will reign when the battle for power is decided.

Companies that are great innovators have an edge on their competition. That’s why it’s important to understand the concepts of what they do – and the value of the intellectual property they possess – for investment options in any market segment. (A common example is companies that manufacture smart phones.) Sometimes you can also identify companies that produce the tools needed to build that innovation – and therefore additional potential investments (like the companies that make the processors or batteries used to build smart phones). And better yet, when you can identify a company that comprehends the utility of their innovation and can harness its power to cross industries and create more innovation and value, you know you’ve found something special. (Smart phones aren’t just phones anymore – they now proclaim the mantra, “there’s an app for that!” – and deliver it across every industry, and in most every country.) That’s huge market potential, and the impetus to win the throne of command.

TOOLS THAT MAKE

When a company produces not just a product it sells for profit, but a tool other companies buy and use to innovate, it stimulates creativity. And while there’s a delicate balance between protecting proprietary information that gives a company the competitive edge, and providing creators enough access to stimulate this creativity, growth can be exponential. Companies like Apple who find this sweet spot can produce highly desirable, intuitive and user-friendly products (iPods, iPhones, iPads), resulting in a host of other companies and individuals using these products to create their own downstream value (their own apps, utilities, accessories), making the products more desirable and customizable. By introducing 1) ease of use, 2) customization, and 3) application, these companies transform products and devices into tools – which deliver value.

Just like cell phones, technology in healthcare is getting smaller. At the molecular and genetic level, there are numerous techniques, or TOOLS THAT MAKE, covering a spectrum of uses and targets (and often accompanied by litigation over ethics and patents). They employ methods to detect, analyze, sequence, and manipulate genetic material, that impact healthcare, agriculture, engineering, pharmaceutical, and food industries. They do so by:

  • Cloning DNA – making copies
  • Searching for specific DNA – targeted organisms and threats
  • Sequencing DNA – to determine order/pattern that defines physiological characteristics or processes
  • Manipulating DNA – rearranging, replacing, manufacturing, and splicing

Cloning to engineer characteristics

The bio-engineering tool that produced the first clones gave us not only Dolly the Sheep, but also “smaller” DNA projects like genetically modified organisms (GMO’s) including neon glofish, Genetech’s manufactured insulin, and Monsanto’s hybrid seeds. And this ability to produce altered genes, albeit a still-controversial issue – has yielded one of the greatest impacts (along with massive computing power) on medical research over the last decade. Test subjects like mice and zebrafish have been altered to possess cancerous tumors, specific protein deficiencies, and various other traits in order to experiment and measure the effectiveness of treatments. No longer is it necessary to selectively breed species to achieve the desired characteristics; they can be engineered.

Searching by amplifying

Polymerase Chain Reaction (PCR) is a technique that melts and separates DNA into its two strands, uses primers and enzymes to select specific sections/targets and replicate the pattern, and then cycle the fragments through a series of heating and cooling steps to amplify and detect if the target DNA is present. This can reveal a particular organism, often used to rapidly and definitively identify bacteria and viruses. Days needed to identify organisms grown on petri plates in the lab, or the antibodies our bodies produce in response to infection, can be reduced to just a few hours instead. Small quantities of organisms (dead or alive), can be detected, along with genes that reveal antibiotic resistance and sub-types (useful in tracking epidemics).

Companies like Cepheid and Nanosphere have created test platforms like GeneXpert and Verigene that can rapidly identify organisms responsible for infectious disease (including hospital and community-acquired), public health threats (potential outbreaks of highly contagious diseases), and safety threats (bioterrorism).  These technologies are being expanded with detection methods that include a panel or array of multiple organisms (respiratory, gastrointestinal, and blood stream infections) to aid in quick identification—important for timely diagnoses like sepsis. Another company in this arena is bioMerieux (which acquired Biofire’s FilmArray in 2014).

Sequencing and patterns

Isolating specific patterns of DNA can aid in detection and identification of a species. What started with “mapping” genetic information of single-celled organisms using PCR to detect the presence of bacteria, culminated with the Human Genome Project, revealing information that continues to help scientists explain disease and target research. Methods like Next-Gen Sequencing (NGS) tackle complex organisms—like humans—to sort, sequence, and/or quantify DNA to detect variations/mutations. Common sequencing tests include non-invasive prenatal testing like Sequenom’s MaterniT21, Verinata Health’s (Illumina) verifi, Natera’s Panorama, and Roche/Ariosa’s Harmony, that use maternal blood to check DNA/chromosomes which reveal the sex of the fetus and possible anomalies that correlate to genetic diseases and birth defects. Pharmaco-kinetics/genetics analyze DNA (how each individual metabolizes specific drugs) so physicians can assess appropriate prescription choices and dosage for blood thinners, statins, pain management, and psychotropic drugs. And bio-markers (genes or tumors) can aid oncologists and pathologists in determining treatments based on the specific marker(s) present and how these correlate to the effectiveness of chemotherapies—personalized medicine.

These sequencing tools can be used to create genetic “blueprints” of the DNA that makes up an entire genome for a species, or the exome (portion of the blueprints that details how proteins are built). The resulting data is not only personalized medicine to determine individual treatments, but also tools to better facilitate research, ways to manipulate DNA, and opportunities to capture and correlate information about genes, treatments, and patient outcomes – as well as environment and lifestyle through studies like California’s Genetic Epidemiology Research on Adult Health and Aging (GERA), a collaboration between the Kaiser Permanente and the Institute for Human Genetics.

Manipulating potential

If we take the science and informatics and apply statistical methods, not only do we get the anthropology, epidemiology, and population health management, we also get the patterns in the code of the data. Not just sequences that display mutations, but the patterns that identify Clustered Regularly Inter-Spaced Palindromic Repeats (CRISPR’s)—that allow DNA to be added or removed. And while this has been a controversial topic with moral, ethical, and legal ramifications of manipulating life (altering organisms, determining sex, and opening the door for eugenics), it also provides a way to splice DNA and to produce synthetic DNA that can be used in all sorts of research and development to correct defects, improve processes, and solicit specific responses. This provides a valuable tool for efficient testing of possible drug targets—a “power tool” for rapid prototyping—that opens the door for shorter drug development and better defined trials.

Combine a tool like CRISPR with the exponential opportunities afforded from data mining copious amounts of genetic information produced by sequencing, the Human Genome Project and projects like GERA, and several questions arise:

  • How do we analyze it and what does it all mean?
  • Where do we store it and how do we manage and protect it?
  • Who owns it, who has access to it, and how do we respect individual privacy while allowing access to this uber database that can provide answers to medical research we so desperately seek?

These are questions yet to be answered – and that provide ample opportunity for a host of biotech, pharma, diagnostic, and data management companies to thrive.

The battle for power

Not surprisingly, it is in this arena with enormous potential, that litigation over patents, infringement, and intellectual property rights have flourished. Companies (like Editas Medicine, Intellia Therapeutics, and Caribou Biosciences) and individuals (like Feng Zhang, Jennifer Doudna, and Emmanuelle Charpentier) who have developed technologies enabling faster, better, and cheaper methods to manipulate DNA are continually competing for exclusivity and/or lucrative partnerships and agreements. From the 1990’s when Myriad patented the BRCA1 and BRCA2 genes, to the landmark decision of 2013 when the U.S. Supreme Court ruled that human genes cannot be patented but synthetic or composite DNA can be, companies continue to vie for patents – right to the discoveries used in research, drug development, and proprietary diagnostic testing—that prevent competitors from capitalizing on their expansive/expensive investments made in research and development.

For more details on the CRISPR battle, who prevails, and how to capitalize on companies benefiting from the technologies and research, while avoiding investment dangers, stay tuned.

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