Genes, the fundamental code of life, are written in DNA (deoxyribonucleic acid). Before DNA was even discovered, humans sought to manipulate genes through selective breeding. Since its discovery, scientists, science fiction writers, philosophers, and others have speculated on the implications of being able to modify DNA. Over the last half century, billions of dollars and immeasurable effort have been devoted to understanding, characterizing, and controlling DNA. This report describes a gene editing technology, known as CRISPR-Cas9, with the potential to revolutionize genetic engineering and the biotechnology industry. The report then provides information on the potential economic benefits of the technology and identifies some issues for congressional consideration, including the regulation of current and future products, national security concerns, and ethical and societal issues surrounding the use of the technology.


What Is CRISPR-Cas9?

CRISPR-Cas9 is a gene editing technology that offers the potential for substantial improvement over other gene editing technologies1 in ease of use, speed, efficacy, and cost. These characteristics led Science magazine to name CRISPR-Cas9 gene editing technology “Breakthrough of the Year” in 2015.2 Many in the scientific, engineering, and business communities believe that CRISPR-Cas9 may offer revolutionary advances in the investigation, prevention, and treatment of diseases; understanding of gene function; improving crop yields and developing new varieties; production of chemicals used in biofuels, adhesives, and fragrances; and control of invasive species.3
CRISPR is an acronym for “clustered regularly interspaced short palindromic repeats,” which are unique DNA sequences found in some bacteria and other microorganisms. These sequences, along with the genes that are located next to them, known as CRISPR-associated or Cas genes, form an immune system that protects against viruses and other infectious DNA. The CRISPR system identifies, cuts, and destroys foreign DNA. Researchers have identified five different types of CRISPR systems. The most studied CRISPR system is associated with the Cas9 protein and is known as CRISPR-Cas9. During 2012 and 2013, researchers modified CRISPR-Cas9 to serve as an effective and efficient technology for editing the genomes4 of plants, animals, and microorganisms. Since then, CRISPR-Cas9 has been used to modify the genomes of a variety of species—ranging from mice and fruit flies to corn and yeast. Many in the scientific community believe CRISPR-Cas9 has shifted the paradigm with its simplicity and low cost relative to other methods of gene editing—removing barriers to widespread adoption and creating new research opportunities.5 This report focuses on the use of CRISPR-Cas9 as a gene editing technology,which is sometimes referred to as CRISPR in the report. However, other CRISPR systems are currently in development and use.

Despite this promise, technical challenges to realizing the full potential of CRISPR-Cas9 remain. Researchers largely agree that efficiently delivering the technology to particular cells, tissues, or organs, and reducing off-target activity (i.e., the number of unintended genetic changes) are among the most pressing challenges. Off-target activity may increase the risk of cancer, and thus improved delivery and specificity are especially important for the development of gene therapy applications.7 Scientists are investigating ways to overcome these challenges and improve CRISPR-Cas9.

Gene Editing

For decades, scientists have altered genes using radiation or chemicals. These methods produce unpredictable results. The invention of recombinant DNA technology in the 1970s allowed scientists to insert new DNA into genes in a directed way, but inserting a specific gene or sequence within the genome remained technically challenging and imprecise.
Gene editing is a newer technique that is used to make specific and intentional changes to DNA.8 Gene editing can be used to insert, remove, or modify DNA in a genome. All gene editing technologies involve an enzyme known as a nuclease for cutting the DNA, in addition to a targeting mechanism that guides the enzyme to a specific location on the DNA strand (i.e., a gene within the genome). Gene editing has traditionally involved the insertion, removal, or modification of a single gene, but with CRISPR-Cas9 multiple genes can be targeted simultaneously. Such multi-gene editing is generally referred to as genome editing.

How CRISPR-Cas9 Technology Works

CRISPR-Cas9 is a gene editing technology that uses a combination of (1) an enzyme that cuts DNA (Cas9, a nuclease) and (2) a guiding piece of genetic material (guide RNA) to specify the location in the genome. Generally, the guide RNA targets and binds to a specific DNA sequence, and the attached Cas9 enzyme cleaves both strands of DNA at that site. This cut can be used to insert, remove, or edit the DNA sequence. The cut is then repaired and the changes incorporated (Figure 1). This specificity of modification is one feature that differentiates CRISPR-Cas9 from predecessor genome editing systems.

Scientists can create a guide RNA corresponding to almost any sequence within an organism’s genome. This flexibility allows for the potential application of the technique to a very wide range of genomes, including microorganisms, animals, or plants. If the sequence of the desired target or gene (and its function) is known, in theory, CRISPR-Cas9 could be used to alter the function of a cell or organism.

The basic CRISPR-Cas9 technology, specifically the Cas9 nuclease, has also been adapted by researchers to allow for additional modifications to the genome beyond the cutting of both strands of the DNA. For example, researchers have adapted Cas9 so that it can be used to change a single base in a gene (base editing), cut a single strand of DNA, or activate or repress the expression of a gene (i.e., increase or decrease the production of a molecule, typically a protein).

What Are Gene Drives?

CRISPR-Cas9 has led to recent breakthroughs in gene drive research. A gene drive is a system of biasing inheritance to increase the likelihood of passing on a modified gene. Offspring inherit one copy of each gene from its parents. Normally, this limits the total incidence of mutations over generation. Gene drive components cause the modified DNA to copy itself into the DNA from the unmodified parent. The result is the preferential increase in a specific trait from one generation to the next and, in time, possibly throughout the population. CRISPR- Cas9 has allowed researchers to more effectively insert a modified gene and the gene drive components. Gene drives have been suggested as a way to eliminate or reduce the transmission of disease, eradicate invasive species, or reverse pesticide resistance in agriculture. The self-propagating nature of gene drives is also accompanied by concerns.

CRISPR-Cas9 Market Projections, Investments, and R&D Spending

CRISPR-Cas9 technology is still in its infancy, with many of the hoped-for applications potentially years in the future. However, the interest, efforts, and investments of the industrial and financial communities suggest the potential economic and other societal benefits are substantial. Among the early indicators of the potential value of CRISPR-enabled products are fees being paid to license CRISPR patents, investments in firms with potential interests in CRISPR intellectual property, the type of companies investing in CRISPR research, and early applications. This section discusses recent projections made by market research firms, select private investments, federal research and development funding, and statistics on scientific publications.

Market Projections

A number of research firms have published market projections for gene editing, including CRISPR-Cas9 and other technologies. Application areas include human therapeutics, research tools, crops, livestock, yogurts, cheeses, and more.

In August 2018, Ireland-based Research and Markets estimated that the global market for gene editing will grow at a compound annual growth rate (CAGR) of 33.26% from $551.2 million in 2017 to $3.087 billion in 2023.11 An earlier report projected that the North American market will account for the largest share of the gene editing market due to “increasing awareness of technology, proximity of companies, and early adoption of latest treatments.” Asia was expected to be the second-largest market, due to “increasing government funding of research, economic prosperity, early adoption of latest technology and the relaxed regulatory environment.” The European market was projected to be the third- largest market, hampered by “the stringent regulatory environment and slow growth due to the economic crisis.”

 India-based Markets and Markets estimated that the global market for gene editing will increase from $3.19 billion in 2017 to $6.28 billion in 2022, a CAGR of 14.5%. CRISPR technology was expected to be the largest and fastest-growing segment of this market in 2017.13

 Zion Market Research estimated that the CRISPR gene editing market in 2017 was $477 million and projected that it will reach $4.271 billion by 2024, a CAGR of 36.8%.14

 A February 2017 projection by the U.S.-based market research firm Grand View Research anticipates the global market for gene editing will reach $8.1 billion by 2025.

Private Investments

Private investments are a commonly used metric for assessing the economic potential of a technology. Investments are being made by and in companies of varying size and technology maturity that are conducting CRISPR research. In addition, these companies are engaging in a wide range of partnerships. Here are several examples of recent investments in CRISPR-focused gene editing firms:

 Editas Medicine (headquartered in Cambridge, MA) raised approximately $97.5 million in its February 2016 initial public offering. In follow-on offerings in March and December 2017, Editas raised approximately $96.7 million and $57.2 million, respectively. In January 2018, the company completed at-the-market offerings and received net proceeds of approximately $48.5 million.

The firm has licensed CRISPR and other gene editing patent rights from the Broad Institute, the Massachusetts Institute of Technology (MIT), Harvard University, and others.

As of November 15, 2018, the company’s market capitalization was $1.34 billion.18 In March 2017, Editas reportedly entered into an agreement with Irish pharmaceutical company Allergan under which Editas was to receive a $90 million up-front payment for an option to license up to five preclinical programs targeting eye disease.

Editas has also partnered with Juno Therapeutics for cancer-related research using CRISPR; under the terms of the agreement, Juno was to pay Editas an initial payment of $25 million and up to $22 million in research support for three programs over five years.20 Editas has also engaged in a three-year research and development (R&D) collaboration deal with San Raffaele Telethon Institute for Gene Therapy to research and develop next- generation stem cell and T-cell therapies for the treatment of rare diseases.

 CRISPR Therapeutics AG (headquartered in Basel, Switzerland, with R&D operations in Cambridge, MA), a firm founded by early CRISPR pioneer Emmanuelle Charpentier, has raised a total of almost $140 million, including a $38 million B-series round of financing in June 2016.22 The company raised an additional $56 million in its October 2016 initial public offering, followed by $122.6 million in January 2018 and $187.6 million in September 2018 in subsequent offerings.

In addition, in August 2016, CRISPR Therapeutics and pharmaceutical company Bayer AG founded Casebia Therapeutics, a joint research venture “to discover, develop and commercialize new breakthrough therapeutics to cure blood disorders, blindness, and congenital heart disease.” Bayer stated that it will be providing at least $300 million for R&D by the joint venture and that it had taken a $35 million equity stake in CRISPR Therapeutics.23 CRISPR Therapeutics also has collaboration and joint development agreements with Boston-based Vertex Pharmaceuticals to use CRISPR-Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. CRISPR Therapeutics and Vertex have reportedly launched the first in-human clinical trial of CRISPR genome editing technology sponsored by U.S. companies. The trial is testing an experimental therapy for the blood disorder β-thalassemia in Regensburg, Germany. As of November 15, 2018, the company’s market capitalization was $1.89 billion.

 Caribou Biosciences, Inc. (headquartered in Berkeley, CA), a firm founded by Jennifer Doudna and other scientists from the University of California, Berkeley, based on an exclusive license to the CRISPR work of that university and the University of Vienna, raised $30 million in private financing in May 2016.

Examples of other efforts focused on CRISPR technology and the development, application, and commercialization of CRISPR-enabled products include the following:

 In September 2016, agrochemical and agricultural biotechnology corporation Monsanto secured a worldwide non-exclusive license agreement for agricultural applications of CRISPR technology from the Broad Institute. With respect to its intended uses, Monsanto stated, “Genome-editing technology is complementary
to our ongoing discovery research and provides an incredible resource to further unlock our world-leading germplasm and genome libraries.”

 Calyxt, Inc. (formerly Cellectis Plant Sciences, Inc., headquartered in New Brighton, MN), has exclusive rights to a group of patents owned by the University of Minnesota for engineering plant genomes with a focus on products such as low trans-fat soybean oil, cold storable potato, gluten reduced wheat, and low saturated canola oil for the food and agriculture industries.

Federal R&D Funding and Scientific Publications

The potential of CRISPR-Cas9 gene editing is further reflected in the rapid increase in CRISPR- related federal research funding and scientific publications. As shown in Table 1, NIH funding for CRISPR-related research grew from more than $5 million in FY2011 to $1.1 billion in FY2018. Similarly, the number of CRISPR-related scientific publications increased from 87 in 2011 to 3,917 in 2018

Table 1. NIH Funding for CRISPR-Related Research, FY2011-FY2018
in dollars
Source: ( as of November 20, 2018.
Advanced Gene Editing: CRISPR-Cas9

Year Projects Total Funding

2011 7 $5,070,129
2012 9 $7,432,520
2013 30 $12,505,507
2014 161 $85,298,742
2015 551 $267,055,410
2016 1,245 $603,205,999
2017 2,031 $947,465,783
2018 2,651 $1,155,385,840
Total 6,685 $3,083,419,930

The Coordinated Framework for the Regulation of Biotechnology

The fundamental federal guidance for regulating biotechnology products, including those developed using CRISPR-Cas9, is the Coordinated Framework for the Regulation of Biotechnology (the Coordinated Framework), originally published in 1986 by the White House Office of Science and Technology Policy (OSTP).30 A key principle in this regulatory structure is that genetically engineered products should continue to be regulated according to their characteristics and unique features, not their production method—that is, whether or not they were created through genetic engineering techniques (e.g., CRISPR-Cas9, ZFNs, and TALENs). The framework provides a regulatory approach intended to ensure the safety of biotechnology research and products, using existing statutory authority and previous agency experience. The Coordinated Framework consists of three primary agencies—the Environmental Protection Agency (EPA), the U.S. Department of Agriculture (USDA), and the Food and Drug Administration (FDA).

 EPA protects human health and the environment by regulating genetically engineered products that qualify as pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act (7 U.S.C. §136 et seq.); it sets guidelines on the amount of pesticidal residue that may be present in food under Section 408 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. §301 et seq.); and it regulates new chemical substances derived from microbial biotechnology under the Toxic Substances Control Act (15 U.S.C. §2601 et seq.).

 USDA regulates biotechnology products that may pose a risk to agricultural plant and animal health under the Plant Protection Act (7 U.S.C. §7701 et seq.) and the Animal Health Protection Act (7 U.S.C. §8301 et seq.).

 FDA protects human health and safety by regulating human and animal drugs, human and animal foods derived from genetically engineered plants, and genetically engineered animals under the authorities of the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act (42 U.S.C. §201 et seq.).
New biotechnology developments, continuing opposition by consumer groups and environmentalists, and perceived inadequacies of federal regulation led the Obama Administration to issue a memorandum on July 2, 2015, to update the Coordinated Framework to ensure that the regulatory structure is capable of meeting future biotechnology risks.

The memorandum observed that each of the federal agencies regulating biotechnology had developed its own regulations and guidance documents to implement its authority under current statutes, resulting in “a complex system for assessing and managing health and environmental risks of the products of biotechnology.” Since a 1992 update, advances in science and technology have “dramatically altered the biotechnology landscape,” according to the memorandum. CRISPR-Cas9 and other gene-editing systems were unknown when the Coordinated Framework was published in 1986, or at the time of the 1992 update.32 The White House memorandum stated that a new update to the Coordinated Framework was needed to “facilitate the appropriate federal oversight by the regulatory system and increase transparency while continuing to provide a framework for advancing innovation.”

The White House memorandum initiated a process to achieve the following objectives: (1) update the Coordinated Framework to clarify the agencies’ roles and responsibilities to regulate biotechnology products; (2) formulate a long-term strategy to ensure that the regulatory system can adequately assess any risks associated with future products of biotechnology while “increasing transparency and predictability and reducing unnecessary costs and burdens”; and (3) commission an external, independent analysis of the future landscape of biotechnology products.

The White House memorandum established a Biotechnology Working Group (BWG) under the Emerging Technologies Interagency Policy Coordination Committee. The working group included representatives of the White House, EPA, FDA, and USDA. The update to the Coordinated Framework by the three primary regulatory agencies overseeing biotechnology was published in January 2017 following three public comment sessions.33 The 2017 update discussed the roles of the three agencies and the coordination of oversight responsibilities. The update generally concluded that the existing structure of regulation among the three agencies remained sound with respect to protecting health and the environment. However, the update did note that uncertainty with respect to agency jurisdiction, and a lack of predictability of timeframes for review, imposed costs on small and mid-size companies and academe. In reinforcing the logic of the 1986 Coordinated Framework, the update also explicitly stated that the “specific regulatory path (and relevant procedures) applicable to any product, including a biotechnology product, is dependent on the nature and characteristics of the product and its application.”

To achieve the second objective of proposing a long-term strategy for biotechnology product regulation, the BWG published the National Strategy for Modernizing the Regulatory System for Biotechnology Products in September 2016.35 The goal of the proposed national strategy is to ensure that the regulatory agencies can “efficiently assess risks of future biotechnology products while supporting innovation, protecting health and the environment, promoting public confidence in the regulatory process, increasing transparency and predictability, and reducing unnecessary costs and burdens.”

To assess the future landscape of biotechnology products, EPA, FDA, and USDA commissioned a study in early 2016 by the National Academy of Sciences (NAS) to identify (1) major advances and potential new types of biotechnology products over the next 5 to 10 years, (2) potential future products that might pose a different type of risk relative to existing products and organisms, (3) areas in which the risks or lack of risk relating to biotechnology are well understood, and (4) the scientific capabilities, tools, and expertise that may be useful to the regulatory agencies as they oversee potential future products of biotechnology. The NAS published its final report in February 2017, emphasizing that the new products stemming from genomic research could overwhelm the three lead regulatory agencies, and outlining a strategic approach to risk management and coordination among these regulatory agencies.36
Despite recent efforts to update the Coordinated Framework, CRISPR-Cas9 technology and other gene-editing systems raise substantive questions about how (or whether) the products resulting from these technologies are to be regulated, and if so, under what statutory authorities. Specifically, the 2017 NAS report found that “regulators will face difficult challenges as they grapple with a broad array of new types of biotechnology products—for example, cosmetics, toys, pets, and office supplies—that go beyond contained industrial uses and traditional environmental release.”37 Some of the products that are likely to be developed using CRISPR- Cas9 will not fit neatly into the established categories that regulatory agencies worldwide have developed over the past 30 years. Potential issues for consideration when developing regulations for biotechnology products developed using CRISPR-Cas9 are discussed in more detail later.

Application Areas and Issues for Consideration

The following sections provide examples of the current and potential uses of CRISPR-Cas9 across a broad set of areas. Some sections include a description of issues for congressional consideration, such as the regulation of future biotechnology products, international implications, and societal, ethical, environmental, and national security concerns.

In July 2017, the Defense Advanced Research Projects Agency (DARPA) announced that the agency would invest $65 million over four years in a program called “Safe Genes” with the goal being to “gain a fundamental understanding of how gene editing technologies function; devise means to safely, responsibly, and predictably harness them for beneficial ends; and address potential health and security concerns related to their accidental or intentional misuse.” According to DARPA, each of the funded research teams will pursue one or more of the following technical objectives:

 develop genetic constructs—biomolecular “instructions”—that provide spatial, temporal, and reversible control of genome editors in living systems;

 devise new drug-based countermeasures that provide prophylactic and treatment options to limit genome editing in organisms and protect genome integrity in populations of organisms; and

 create a capability to eliminate unwanted engineered genes from systems and restore them to genetic baseline states.


Heidi Ledford, “CRISPR, the Disruptor,” Nature, vol. 522, no. 7554, June 3, 2015, pp. 20-24. 4 A genome is an organism’s complete set of DNA, including all of its genes.

Heidi Ledford, “CRISPR, the Disruptor,” Nature, vol. 522, no. 7554, June 3, 2015, pp. 20-24.

Prashant Mali, Kevin M. Esvelt, and George M. Church, “Cas9 as a Versatile Tool for Engineering Biology,” Nature
Methods, vol. 10, no. 10, October 2013, p. 962.

Research and Markets, “CRISPR Market – Forecasts from 2018 to 2023,” August 2018,

Research and Markets, “Genome Editing Global Market-Forecast to 2022,” September 2016,

Markets and Markets, “Genome Editing/Genome Engineering Market Worth 6.28 Billion USD by 2022,” November 2017,

Zion Market Research, “Global CRISPR Genome Editing Market Will Grow USD 4,271.0 Million by 2024,” August 2018, Will-Grow-USD-4-271-0-Million-by-2024-Zion-Market-Research.html.

Grand View Research, “Genome Editing Market Size to Reach $8.1 Billion by 2025,” February 2017,

Security and Exchange Commission, EDGAR database, Editas Medicine, 10-Q, filed November 8, 2018,

Securities and Exchange Commission 10-K filing for the year ending December 31, 2015,

Google Finance, “Editas Medicine, Inc.,” accessed on November 15, 2018, Medicine Enter into Strategic R&D Alliance to Discover and Develop CRISPR Genome Editing Medicines for Eye Diseases,” press release, March 14, 2017, thomson-reuters/allergan-and-editas-medicine-enter-into-strategic.

Juno Therapeutics, Inc., “Juno Therapeutics and Editas Medicine Announce Exclusive Collaboration to Create Next- Generation CAR T and TCR Cell Therapies,” press release, May 27, 2015, c=254265&p=irol-newsArticle&ID=2125229.

Editas Medicine, Inc., “Editas Medicine Announces Scientific Multi-Year Collaboration with Fondazione Telethon and Ospedale San Raffaele,” press release, June 28, 2016, irol-newsArticle&ID=2189488.

CRISPR Therapeutics AG, “CRISPR Therapeutics Raises Additional $38M as Part of Series B Financing,” press release, June 24, 2016,

Prepared remarks of Marijn Dekkers, Chairman of the Board of Management, Bayer AG, February 25, 2016, ccm=040.

Google Finance, “Crispr Therapeutics AG,” accessed on April 17, 2017, NASDAQ:CRSP.

Caribou Biosciences, Inc.,; Caribou Biosciences, Inc., “Caribou Biosciences Raises $30 Million in Series B Funding,” press release, May 16, 2016, releases/caribou-biosciences-raises-30-million-in-series-b-funding.

Preetika Rana, Amy Dockser Marcus, and Wenxin Fan, “China, Unhampered by Rules, Races Ahead in Gene-Editing Trials,” The Wall Street Journal, January 21, 2018, ahead-in-gene-editing-trials-1516562360.

Monsanto Company, “Monsanto Announces Global Licensing Agreement with Broad Institute on Key Genome- Editing Application,” press release, September 22, 2016, announces-global-licensing-agreement-broad-institute-key-genome-edi; Issi Rosen, Chief Business Officer, Broad Institute, “Licensing CRISPR for Agriculture: Policy Considerations,” Broad Institute, news/licensing-crispr-agriculture-policy-considerations.

Calyxt, Inc., “University of Minnesota Grants Calyxt an Exclusive License,” press release, July 28, 2016,

Memorandum for Heads of Food and Drug Administration, Environmental Protection Agency, and Department of Agriculture, “Modernizing the Regulatory System for Biotechnology Products,” Executive Office of the President, July 2, 2015. modernizing_the_reg_system_for_biotech_products_memo_final.pdf.

The discovery of CRISPR occurred at Japan’s Osaka University in 1987, although the implications of the technology for genetic modification of organisms other than microbes were not recognized until researchers at Harvard, Vilnius University, University of California, Berkeley, and the Max Plank Institute in Germany developed a model in 2011- 2012 that permitted genomic engineering of plants and animals. See Doudna, J.A. and Charpentier, E. “The New Frontier of Genome Engineering with CRISPR/Cas9,” Science, vol. 346, issue 6213, November 28, 2014. DOI: 10.1126/science.1258096.

Increasing the Transparency, Coordination, and Predictability of the Biotechnology Regulatory System, January 2017, biotechnology-regulatory. biotechnology-regulatory.

National Academies of Science, Engineering, and Medicine, Preparing for Future Products of Biotechnology, The National Academies Press. DOI:
37 Ibid.