Technology Foresight

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1 Technology Foresight Winter 2016 TF CRISPR Gene Editing A New Age for Genetics SUMMARY In the midst of unprecedented growth in the field of biology, the Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR) system has opened the floodgates on genome modification. CRISPR derives its name from a recurring genetic pattern found in bacterial genomes a pattern of repeating genetic code that plays a vital role in the immune system. Essentially, these repeating segments contain information on how to identify and destroy any bacteria and viruses that an organism has encountered previously. Notably, CRISPR repeating code is found alongside highly specialized proteins known as Cas9, which are able to destroy the genetic code of any bacteria that the repeats designate as a threat. In a potentially revolutionary development, scientists have recently discovered that they are able to use CRISPR not only to destroy viruses and bacteria, but also to target and replace undesirable or damaged portions of the genome with improved healthy segments. 1 Harnessing and employing this methodology will likely revolutionize the ways in which humans interact with the very fabric of biology genetic code. CONTENTS Summary 1 Why it matters 1 Drivers 2 Potential Uses 2 Opportunities 3 Risks 4 Other implications 4 Related forecasts 5 References 5 WHY IT MATTERS The underlying concept of genetic modification has existed for decades, but previous methods proved to be expensive, complicated, and limited in application outside of the laboratory. 2 CRISPR differs from previous applications by way of its modularity, ease of use, precision, and lower costs. Already, CRISPR technologies have been successfully tested on a wide range of plants, animals, bacteria, viruses, and nonviable human embryos. 3 Yet although many of these tests have demonstrated

2 2 positive results, CRISPR is still very much a developing technology. Genetic code is not fully understood and many scientists as well as regulatory bodies are cautious about introducing CRISPR-modified organisms into the environment. Still, numerous biological scientists remain optimistic that, if applied correctly, CRISPR technologies have the potential to provide an easy-to-use, inexpensive, and precise tool that companies and organizations may use in a variety of industries over the coming years. DRIVERS The battle against global epidemics. A combination of growing global population, increased globalization, and shifting climate conditions is elevating the risk of epidemics and pandemics. 5 The attempt to lessen these dangers is driving scientists to seek faster methods to develop cures and immunizations to prevent and/or stem future outbreaks like the 2014 Ebola outbreak. Emerging Cures Using CRISPR, scientists were able to edit and repair the genetic mutations that cause muscular dystrophy in mice. 4 Image: Getty Images Feeding a growing global population. As an ever-growing population strains Earth s natural resources, providing enough food for the public will require increased agricultural yields. The World Bank estimates that by 2050, global food production will need to increase at least 50% over current yields to keep pace with population trends. The World Bank also estimates that the effects of climate change could slash food yields by 25% over the next 30 years. 6 To provide for future generations, agricultural and food scientists are seeking new tools and techniques with the potential to increase yields. Treating an aging population. With global life expectancies on the rise, new technologies aimed not only at extending duration, but also at improving the quality of life will become increasingly paramount. POTENTIAL USES With CRISPR research still in early stages, precisely when, or if, any of these trials will be approved for the general public remains

3 3 unknown. However, several studies have met with positive results and suggest CRISPR could be a powerful tool for functions including: Designer Livestock Combating disease. Researchers have shown that it may be possible to use CRISPR to identify and remove HIV from cells. 8 Additionally, CRISPR gene editing has been used to create mosquitoes that are more resistant to transmitting malaria. 9 Improving food supplies. Agricultural scientists have launched a number of studies aimed at creating plants that are more resistant to disease and harsh climate conditions. 10 Chinese scientists used CRISPR to delete genes that inhibit muscle and hair growth to produce goats that feature larger muscles and longer hair for wool. 11 Creating new cures. Scientists successfully treated lab mice for muscular dystrophy by repairing the gene that expresses the dystrophin protein (which is needed to form healthy muscle cells). 12 While human trials are still far off, blood cancer may be a good candidate for CRISPR applications. The blood can be removed, modified, and analyzed thoroughly before being put back into the body. 13 Making animal organs suitable for human transplants. A Harvard geneticist is modifying genes in pig embryos to make their organs suitable for human transplant. 14 Chinese scientists used CRISPR to delete genes that suppress muscle and hair growth in goats believing this method will be a safe and effective way to boost the sale of goat meat and cashmere sweaters. 7 - Image: Jeff P (flickr) OPPORTUNITIES Applications of CRISPR technology may generate opportunities to create new products, or make existing products more easily, with less waste. Organizations that rely on natural materials should imagine what products could be modified with CRISPR to be made bigger, stronger, faster, or cheaper. CRISPR technologies may be able both to improve crop yields and to reduce the risks of spoilage. Food suppliers could employ these advantages to expand shipping capabilities with less risk of loss. Companies that hope to use CRISPR should consider how to communicate honestly and openly the risks and benefits of the research and application areas being investigated. When

4 4 presented with specific applications of the technology, public opinion moves in favor of genetic modification. Approaches applied to fuels and to medicine are much more likely to win quick acceptance than applications to foods. Medical and drug companies will likely find it beneficial to explore ways in which CRISPR technologies could be used to create new or modified drugs, treatments, and diagnostic tests. CRISPR is an evolving and emerging technology. Building a portfolio of partnerships with universities and private research labs may be an effective way for larger organizations to make initial investments in the technology. FOR MORE INFORMATION For a customized analysis about what the trends and forecasts in this report could mean for your organization, please contact Michael Vidikan at Michael@futureinfocus.com. RISKS The implications and consequences of human genome editing are still not fully understood. Many scientists have cautioned that altering genes could result in unknown side effects and complications. 15 Negative unforeseen consequences will likely tarnish any companies and brands associated with them. Regardless of possible ethical issues CRISPR editing raises, it will very likely raise a public debate over the extent to which doctors and scientists should be allowed to play God with genetics. Businesses should be prepared to work with ethicists and seek common ground with those who have ethical issues about the uses of this technology; bridging these issues will be crucial, independent of early successes or failures. Governments and other regulatory bodies have yet to decide to what extent genetic modification will be legally permitted. Organizations considering using or investing in this technology should keep a keen eye on the regulatory climate. OTHER IMPLICATIONS If CRISPR gene editing reduces the costs of genetic modification, small biology labs may develop the capability to compete with large, established firms. This could provide increased investment opportunities and foster competition in biomedical industries. 16

5 5 Since CRISPR gene edits are inheritable, organisms released into the wild with certain gene edits could radically change, or even eradicate, species. 17 Through CRISPR technologies, small labs may soon be able to perform complex gene edits on bacteria and viruses. This heightens the potential for violent regimes and terrorist organizations to harness gene editing to create unknown bioweapons. RELATED FORECASTS TF Microbiome discusses the study of bacteria and other organisms living on and in the human body and its role in advancing medicine. TF DIY Biotech explores the movement of biohackers, individuals and groups engaged in biotech outside traditional laboratories, which has become known as garage biology. TF Synthetic Biology Update explores recent advances in synthetic biology which may allow scientists to create or modify biological parts and organisms. REFERENCES 1 Sarah Zhand, Everything You Need to Know about CRISPR, the New Tool that Edits DNA, May 6, 2015, 2 David Benjamin, Turitz Cox, Randall Jeffrey Platt, & Feng Zhang, Therapeutic Genome Editing: Prospects and Challenges, February 2015, Nature Medicine, 3 Daneshvar Kaveh, CRISPR-Cas9 in Gene Therapy: Much Control on Breaking, Little Control on Repairing, May 28, 2015, 4 Sokol Natasha, Global Trends in Human Infectious Disease: Rising Number of Outbreaks, Fewer Per-Capita Cases, November 4, 2014, 5 Sokol Natasha, Global Trends in Human Infectious Disease: Rising Number of Outbreaks, Fewer Per-Capita Cases, November 4, 2014,

6 6 6 Food Security Overview, World Bank, April 1, 2015, 7 Christina Larson, China's Bold Push into Genetically Customized Animals, November 17, 2015, Scientific American. 8 Jay Bennett, 11 Crazy Gene-Hacking Things We Can Do with CRISPR, January 26, 2016, 9 Dana Dovey, Gene Editing Mosquitoes with CRISPR Technology Could Eliminate Threat 0f Malaria and Other Tropical Diseases, May 26, 2015, 10 Selle Kurt & Barrangou Rodolphe, CRISPR-Based Technologies and the Future of Food Science, November 2015, Journal of Food Science Volume 80 Issue Jay Bennett, China Used Gene-Editing to Make Hulked-Out Goats and Dogs. Where Does It End? November 18, 2015, 12 Jay Bennett, 11 Crazy Gene-Hacking Things We Can Do with CRISPR, January 26, 2016, 13 Carina Storrs, Could the DNA-Editing CRISPR Revolutionize Medicine? August 12, 2015, 14 Tanya Lewis, Scientists May Soon Be Able to 'Cut and Paste' DNA to Cure Deadly Diseases and Design Perfect Babies, November 19, 2015, 15 CRISPR/Cas9 and Targeted Genome Editing: A New Era in Molecular Biology, 2014, New England Biolabs, 16 Experts Debate: Are We Playing with Fire When We Edit Human Genes, November 17, 2015, 17 Selle Kurt & Barrangou Rodolphe, CRISPR-Based Technologies and the Future of Food Science, November 2015, Journal of Food Science Volume 80 Issue 11.