CRISPR is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. These sequences are derived from DNA fragments of bacteriophages that had previously infected the prokaryote. They are used to detect and destroy DNA from similar bacteriophages during subsequent infections. Hence these sequences play a key role in the antiviral defense system of prokaryotes and provide a form of acquired immunity. CRISPR is found in approximately 50% of sequenced bacterial genomes and nearly 90% of sequenced archaea.
Guide RNA (gRNA) or single guide RNA (sgRNA) is a short sequence of RNA that functions as a guide for the Cas9-endonuclease or other Cas-proteins that cut the double-stranded DNA and thereby can be used for gene editing. In bacteria and archaea, gRNAs are a part of the CRISPR-Cas system that serves as an adaptive immune defense that protects the organism from viruses. Here the short gRNAs serve as detectors of foreign DNA and direct the Cas-enzymes that degrades the foreign nucleic acid.
Jennifer Anne Doudna is an American biochemist who has pioneered work in CRISPR gene editing, and made other fundamental contributions in biochemistry and genetics. Doudna was one of the first women to share a Nobel in the sciences. She received the 2020 Nobel Prize in Chemistry, with Emmanuelle Charpentier, "for the development of a method for genome editing." She is the Li Ka Shing Chancellor's Chair Professor in the department of chemistry and the department of molecular and cell biology at the University of California, Berkeley. She has been an investigator with the Howard Hughes Medical Institute since 1997.
The Plants for Human Health Institute (PHHI) is a North Carolina State University based research and education organization located at the North Carolina Research Campus in Kannapolis, North Carolina, United States. The PHHI researches food crops, like fruits and vegetables, and the potential health-promoting properties they may convey when consumed.
Cas9 is a 160 kilodalton protein which plays a vital role in the immunological defense of certain bacteria against DNA viruses and plasmids, and is heavily utilized in genetic engineering applications. Its main function is to cut DNA and thereby alter a cell's genome. The CRISPR-Cas9 genome editing technique was a significant contributor to the Nobel Prize in Chemistry in 2020 being awarded to Emmanuelle Charpentier and Jennifer Doudna.
Feng Zhang is a Chinese–American biochemist. Zhang currently holds the James and Patricia Poitras Professorship in Neuroscience at the McGovern Institute for Brain Research and in the departments of Brain and Cognitive Sciences and Biological Engineering at the Massachusetts Institute of Technology. He also has appointments with the Broad Institute of MIT and Harvard. He is most well known for his central role in the development of optogenetics and CRISPR technologies.
CRISPR interference (CRISPRi) is a genetic perturbation technique that allows for sequence-specific repression of gene expression in prokaryotic and eukaryotic cells. It was first developed by Stanley Qi and colleagues in the laboratories of Wendell Lim, Adam Arkin, Jonathan Weissman, and Jennifer Doudna. Sequence-specific activation of gene expression refers to CRISPR activation (CRISPRa).
CRISPR-Cas design tools are computer software platforms and bioinformatics tools used to facilitate the design of guide RNAs (gRNAs) for use with the CRISPR/Cas gene editing system.
Emmanuelle Marie Charpentier is a French professor and researcher in microbiology, genetics, and biochemistry. As of 2015, she has been a director at the Max Planck Institute for Infection Biology in Berlin. In 2018, she founded an independent research institute, the Max Planck Unit for the Science of Pathogens. In 2020, Charpentier and American biochemist Jennifer Doudna of the University of California, Berkeley, were awarded the Nobel Prize in Chemistry "for the development of a method for genome editing". This was the first science Nobel Prize ever won by two women only.
Philippe Horvath is a French scientist working for DuPont Nutrition and Health. His work was integral to the development of CRISPR-Cas, a versatile biochemical method for targeted genetic engineering. For this work, he was awarded the 2015 Massry Prize along with Emmanuelle Charpentier and Jennifer Doudna, as well as the 2016 Canada Gairdner International Award, with his Massry co-laureates in addition to Feng Zhang, Rodolphe Barrangou, Anthony Fauci, and Frank Plummer.
J. Keith Joung is an American pathologist and molecular biologist who holds the Robert B. Colvin Endowed Chair in Pathology at Massachusetts General Hospital and is Professor of Pathology at Harvard Medical School. He is a leading figure in the field of genome editing and has pioneered the development of designer nucleases and sensitive off-target detection methods.
CRISPR-Display (CRISP-Disp) is a modification of the CRISPR/Cas9 system for genome editing. The CRISPR/Cas9 system uses a short guide RNA (sgRNA) sequence to direct a Streptococcus pyogenes Cas9 nuclease, acting as a programmable DNA binding protein, to cleave DNA at a site of interest.
Human germline engineering is the process by which the genome of an individual is edited in such a way that the change is heritable. This is achieved by altering the genes of the germ cells, which then mature into genetically modified eggs and sperm. For safety, ethical, and social reasons, there is broad agreement among the scientific community and the public that germline editing for reproduction is a red line that should not be crossed at this point in time. There are differing public sentiments, however, on whether it may be performed in the future depending on whether the intent would be therapeutic or non-therapeutic.
Intellia Therapeutics, Inc. is an American clinical-stage biotechnology company focused on developing novel, potentially curative therapeutics leveraging CRISPR-based technologies. The company's in vivo programs use intravenously administered CRISPR as the therapy, in which the company's proprietary delivery technology enables highly precise editing of disease-causing genes directly within specific target tissues. Intellia's ex vivo programs use CRISPR to create the therapy by using engineered human cells to treat cancer and autoimmune diseases.
Off-target genome editing refers to nonspecific and unintended genetic modifications that can arise through the use of engineered nuclease technologies such as: clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9, transcription activator-like effector nucleases (TALEN), meganucleases, and zinc finger nucleases (ZFN). These tools use different mechanisms to bind a predetermined sequence of DNA (“target”), which they cleave, creating a double-stranded chromosomal break (DSB) that summons the cell's DNA repair mechanisms and leads to site-specific modifications. If these complexes do not bind at the target, often a result of homologous sequences and/or mismatch tolerance, they will cleave off-target DSB and cause non-specific genetic modifications. Specifically, off-target effects consist of unintended point mutations, deletions, insertions inversions, and translocations.
Lei "Stanley" Qi is an associate professor in the department of bioengineering, and the department of chemical and systems biology at Stanford University. Qi led the development of the first catalytically dead Cas9 lacking endonuclease activity (dCas9), which is the basis for CRISPR interference (CRISPRi). His laboratory subsequently developed CRISPR-Genome Organization (CRISPR-GO).
CRISPR gene editing is a genetic engineering technique in molecular biology by which the genomes of living organisms may be modified. It is based on a simplified version of the bacterial CRISPR-Cas9 antiviral defense system. By delivering the Cas9 nuclease complexed with a synthetic guide RNA (gRNA) into a cell, the cell's genome can be cut at a desired location, allowing existing genes to be removed and/or new ones added in vivo.
Locus Biosciences is a clinical-stage pharmaceutical company, founded in 2015 and based in Research Triangle Park, North Carolina. Locus develops phage therapies based on CRISPR–Cas3 gene editing technology, as opposed to the more commonly used CRISPR-Cas9, delivered by engineered bacteriophages. The intended therapeutic targets are antibiotic-resistant bacterial infections.
Kiana Aran is a biomedical entrepreneur and Associate Professor at both UC San Diego's School of Medicine and UC San Diego's Jacobs School of Engineering in the Department of Bioengineering. She is also the Chief Innovation Officer at Paragraf Ltd. Paragraf, a UK-based semi-conductor company, acquired Cardea Bio Inc., which she co-founded and ran as the Chief Science Offer. She has also helped co-found CRISPR QC Inc. that offers a CRISPR Analytics Platform that helps pharma and biotech companies optimize their gene editing research. Her overall research and inventions are focused around developing technologies and bioelectronics for multi-omics studies and applications, especially when they enable products and technologies for studying the mechanisms of healthy aging. She became known as the pioneer of fusing CRISPR and electronics, resulting in the CRISPR-chip technology that is being used to improve the quality of genotyping and gene editing. She was awarded the 2021 Nature – Estée Lauder Research Award for Inspiring Women in Science.
