CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, and it is a genetic engineering technology developed to target, edit, and modify genes to treat genetic diseases (Simon, Rodriguez, & Santiago, 2018). This technology could be as revolutionary to genetic diseases as antibiotics were to bacterial infections! This article provides a high-level overview of the technology, discusses the current state of technology use, and describes implications for nursing education and practice.

OVERVIEW

The CRISPR-Cas technology is used to find a specific sequence of DNA responsible for a disease using a guide ribonucleic acid (RNA), cut it out using a Cas protein, and edit the sequence or replace it with a sequence free of disease-causing mutations. CRISPR-Cas technology can only be used if the genetic sequence causing a disease (e.g., sickle cell anemia or cystic fibrosis) has been identified because the technology has to "find" the sequence among the more than 20,000 protein-coding genes in the human body. (Watch the Ted Talk video by Dr. Jennifer Doudna, one of the scientists who discovered CRISPR-Cas in 2012, to understand the technology more fully at https://www.youtube.com/watch?v=TdBAHexVYzc&t=624s.)

The CRISPR-Cas technology has already been used in plant and animal research. For example, agricultural researchers from different universities have use the technology to edit the genes of Indica rice to improve the yield of the plant; soybeans to cause late flowering that increases the size of the plant; and oranges to make the plants resistant to citrus canker (Svitashev et al., 2015). Other plants modified using CRISPR-Cas include tomatoes, corn, sorghum, and wheat. CRISPR-Cas research in animals has focused on making animals such as pigs resistant to infections. Other researchers are working on making hypoallergenic eggs from chickens to enable humans to take egg-based vaccinations; hygienic bees that clean their habits so the bee population can be replenished; and malaria-resistant mosquitoes to reduce the incidence of malaria in the human population.

The most important use of CRISPR-Cas in animals is to model diseases and study the effect of CRISPR modifications before human trials start (Reardon, 2016). For example, scientists have introduced lung, liver, and pancreatic cancers, inherited cardiomyopathy, and inherited eye diseases in mice so the diseases and potential treatments can be studied (Li et al., 2019). CRISPR-Cas was used in pigs to induce Huntington's disease, a neurodegenerative disease with no effective treatment. A major breakthrough was made when the team introduced a "knock-out" gene (replacing the mutated genetic sequence) to treat the disease. Although not tested in humans yet, this discovery could lead to drug therapy to treat and cure this debilitating disease (Li et al. 2019).

STATE OF THE TECNHOLOGY

Universities and start-up companies are leading the innovations in medical treatment of humans with CRISPR-Cas technology. Applications for patents rose dramatically between 2012 and 2017 with 75 patents already issued in the United States (Kwon, 2019). The initial technology used a protein called Cas-9 to cut the genetic sequence. However, more than 50 enzymes from the Cas system have been discovered, which could lead to more innovations in the technology (Kwon, 2019).

Until recently, sequences had to be edited one at a time. However, a team at ETH Zurich, a university in Switzerland, has developed a CRIPR-Cas technique to edit over a dozen sequences at once, which will increase the efficacy of future treatments (ETH Zurich, 2019). A team of researchers from MIT and Harvard is developing a CRISPR process to edit DNA gels for use in diagnostic devices and medications (Irving, 2019). The group tested the CRISPR-Cas12a with blood samples containing Ebola virus RNA, and the device was able to detect the presence of this virus in the blood. Other infectious diseases could be found in blood using the same technology, and the diagnostic testing could be done in office settings (Irving).

To date, clinical trials in humans have been approved for investigations of recurrent cancer (multiple myeloma and sarcoma), sickle-cell disorder and beta-thalassemia, and Leber congenital amaurosis, the most common type of inherited blindness in children (Saey, 2019). While the scientific community is rightly excited by the technology, it is too soon to know the long-term consequences of CRISPR-Cas technology. In addition, ethical issues about this gene-editing tool cannot be ignored, particularly as they relate to treatment in the prenatal period.

IMPLICATIONS FOR NURSES

Nurses and advanced practice nurses must become more educated about genetics and genomes because of CRISPR-Cas and other rapidly developing technologies. In order for students to become literate in genomics, nursing faculty must be knowledgeable. A study of knowledge of nursing faculty on the Genomic Nursing Concept Inventory (GNCI) showed faculty got less than half of the answers correct (Read & Ward, 2015). It is not surprising genomic literacy, as measured by the GNCI, was similarly poor among baccalaureate nursing students (Ward et al., 2016). The call for genetics and genomics to be in nursing curricula dates back to the early 2000s (Berry & Hern, 2004) but little progress has been made.

In 2009, the American Nurses Association published its second edition of Essentials of Genetic and Genomic Nursing, developed by consensus to guide nursing education and practice and available online at no cost (https://www.genome.gov/Pages/Careers/HealthProfessionalEducation/geneticscompete). After this document was published, more advances in technology to sequence genomes have revealed the genetic role in medications; pharmacogenomic information is available in 80 percent of "prescribing information" for medications (Montgomery, 2017). Some medications are directly affected by a person's genes: opioid effectiveness, antidepressant response, stain safety, warfarin sensitivity, and bronchodilator desensitization (Berry & Hearn, 2004; Montgomery, 2017). Hepatic iosenzymes affect the metabolism of medications, and many genetic variants interfere with drug metabolism, which creates potential adverse drug reactions. Clearly these examples show the need for genetic and genomic nursing knowledge in current practice.

In terms of CRISPR-Cas technology, nurses will monitor patients to assess for the effectiveness of treatments, unintended effects on other parts of the body, and manifestations of errors in the application of CRISPR-Cas technology such as cutting in the wrong location or replacing the genetic sequence incorrectly. In addition, nurses will need to assess for manifestations indicating the completeness of treatment with CRISPR-Cas because the gene editing could affect a portion of the genome rather than 100 percent of targeted sequences. The knowledge of genetics, genomic treatments and effects, and the nurse's role in patient care with CRISPR-Cas treatment needs to become mainstream in nursing undergraduate and graduate education. Interested readers can explore more at the website of the International Society of Nurses in Genetics, which is found at https://www.isong.org.

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