Science.org
written by Joy Y. Wang and Jennifer A. Doudna
January 20, 2023
A decade of CRISPR
In the decade since the publication of CRISPR-Cas9 as a genome-editing technology, the CRISPR toolbox and its applications have profoundly changed basic and applied biological research. Wang and Doudna now review the origins and utility of CRISPR-based genome editing, the successes and current limitations of the technology, and where innovation and engineering are needed. The authors describe important advances in the development of CRISPR genome-editing technology and make predictions about where the field is headed. They also highlight specific examples in medicine and agriculture that show how CRISPR is already affecting society, with exciting opportunities for the future. —DJ
Structured Abstract
BACKGROUND
The fields of molecular biology, genetics, and genomics are at a critical juncture—a moment in history when a convergence of knowledge and methods has made it both technically possible and incredibly useful to edit specific base pairs or segments of DNA in cells and living organisms. The advent of clustered regularly interspaced short palindromic repeat (CRISPR) genome editing, coupled with advances in computing and imaging capabilities, has initiated a new era in which we can not only diagnose human diseases and even predict individual susceptibility based on personal genetics but also act on that information. Likewise, we can both identify and rapidly alter genes responsible for plant traits, transforming the pace of agricultural research and plant breeding. The applications of this technology convergence are profound and far reaching—and they are happening now. In the decade since the publication of CRISPR-Cas9 as a genome editing technology, the CRISPR toolbox and its applications have profoundly changed biological research, impacting not only patients with genetic diseases but also agricultural practices and products. As a specific example from the field of genomic medicine, it has become feasible to obtain a complete sequence of the human genome in less than 24 hours—a staggering advance considering the first such sequence took 5 years to generate. Notably, designing and putting to use a potent CRISPR genome editor to obtain clinically actionable information from that genome—previously a near-intractable challenge—now takes only a matter of days. For additional background and related topics, we refer readers to in-depth reviews of the microbiology and structural biology of CRISPR systems and to articles about the considerable ethical and societal challenges of this technology.
ADVANCES
The past decade has witnessed the discovery, engineering, and deployment of RNA-programmed genome editors across many applications. By leveraging CRISPR-Cas9’s most fundamental activity to create a targeted genetic disruption in a gene or gene regulatory element, scientists have built successful platforms for the rapid creation of knockout mice and other animal models, genetic screening, and multiplexed editing. Beyond traditional CRISPR-Cas9–induced knockouts, base editing—a technology utilizing engineered Cas9’s fused to enzymes that alter the chemical nature of DNA bases—has also provided a highly useful strategy to generate site-specific and precise point mutations. Over the past decade, scientists have utilized CRISPR technology as a readily adaptable tool to probe biological function, dissect genetic interactions, and inform strategies to combat human diseases and engineer crops. This Review covers the origins and successes of CRISPR-based genome editing and discusses the most pressing challenges, which include improving editing accuracy and precision, implementing strategies for precise programmable genetic sequence insertions, improving targeted delivery of CRISPR editors, and increasing access and affordability. We examine current efforts addressing these challenges, including emerging gene insertion technologies and new delivery modalities, and describe where further innovation and engineering are needed. CRISPR genome editors are already being deployed in medicine and agriculture, and this Review highlights key examples, including a CRISPR-based therapy treating sickle cell disease, a more nutritious CRISPR-edited tomato, and a high-yield, disease-resistant CRISPR-edited wheat, to illustrate CRISPR’s current and potential future impacts in society.
OUTLOOK
In the decade ahead, genome editing research and applications will continue to expand and will intersect with advances in technologies, such as machine learning, live cell imaging, and sequencing. A combination of discovery and engineering will diversify and refine the CRISPR toolbox to combat current challenges and enable more wide-ranging applications in both fundamental and applied research. Just as during the advent of CRISPR genome editing, a combination of scientific curiosity and the desire to benefit society will drive the next decade of innovation in CRISPR technology.
Abstract
The advent of clustered regularly interspaced short palindromic repeat (CRISPR) genome editing, coupled with advances in computing and imaging capabilities, has initiated a new era in which genetic diseases and individual disease susceptibilities are both predictable and actionable. Likewise, genes responsible for plant traits can be identified and altered quickly, transforming the pace of agricultural research and plant breeding. In this Review, we discuss the current state of CRISPR-mediated genetic manipulation in human cells, animals, and plants along with relevant successes and challenges and present a roadmap for the future of this technology.
CRISPR: past, present, and future.
The past decade of CRISPR technology has focused on building the platforms for generating gene knockouts, creating knockout mice and other animal models, genetic screening, and multiplexed editing. CRISPR’s applications in medicine and agriculture are already beginning and will serve as the focus for the next decade as society’s demands drive further innovation in CRISPR technology.
🚨👇AS YOU CAN CLEARLY SEE, I DID NOT ALTER THE ORIGINAL VIDEO. THE INSTAGRAM VIDEO I SHARED IBELOW S THE SAME VIDEO AS THE DFID TWEET ABOVE THAT I COPIED AND I DID NOT WRITE A VIDEO DESCRIPTION EITHER.👇🚨
However, the stupid fact checkers claimed my post is false and now I'm highly restricted on Instagram where I can't make any comments or like anything for over a week now. Because of the stupid fact checkers falsely accusing me of making a false post, I'm not able to interact with my Instagram followers. I sent Instagram a request to review this fact check that is wrong. (emphasis mine)
🚨👇FYI 👇🚨
I took this screenshot above to tie it all together.
just type 'covid vaccine crispr' in the Google search for more info.
and lol seeing all the fact checkers saying this is not true they are not editing genes.
I took the screenshots above.
FROM PFIZER WEBSITE: What is Gene Editing? Gene editing is a precise change of a patient’s DNA using site-specific, targeted nucleases (eg, CRISPR, Zinc Finger). This approach either permanently removes or modifies a gene, or adds a functioning gene within the patient’s body. https://www.pfizer.com/science/innovation/gene-therapy/genes-as-medicines
NPR
March 8, 2021
TERRY GROSS, HOST:
This is FRESH AIR. I'm Terry Gross. The Pfizer and Moderna COVID vaccines are the first vaccines to be activated by mRNA. These vaccines build on the breakthroughs of the gene-editing technology known as CRISPR. This technology is also being used to treat people who have sickle cell anemia, certain cancers, Huntington's disease and congenital blindness, and will likely be used to treat many other diseases in the future. There are many other CRISPR-related breakthroughs on the horizon and a lot of moral and ethical questions to deal with about the editing of the basic element of human life.
One of the developers of CRISPR is Jennifer Doudna, who shared a Nobel Prize last year for her discoveries about gene editing. Doudna and the story of RNA-related scientific breakthroughs are the subjects of Walter Isaacson's new book, "The Code Breaker." While writing the book, he became part of a double-blind trial of the Pfizer vaccine. In other words, he was given the vaccine but wasn't told whether it was actually the vaccine or a placebo. Then he was monitored for symptoms of COVID and for side effects of the vaccine. Isaacson is also the author of biographies of Ben Franklin, Steve Jobs, Albert Einstein and Leonardo da Vinci. He's a professor of history at Tulane and was formerly the CEO of the Aspen Institute, chair of CNN and editor of Time magazine.
GROSS: Before we get deep into the science of the vaccine itself, let's do some background science and background history of RNA so it'll make it easier to understand the science of the vaccine. So we're talking here about RNA or, more specifically, mRNA. RNA is a sister of DNA. We know what DNA is kind of. I mean, we know that we can submit our DNA through saliva and find out more about our genealogy. We know if there was a crime, they could take DNA samples and trace who the criminal is through a DNA databank if you're lucky and the DNA is already in the databank. So what is RNA compared to DNA?
ISAACSON: You're right. DNA is the famous sibling. It's the one that gets on the magazine covers. And we talk about the DNA of an organization, of a society. But like a lot of famous siblings, DNA doesn't do a whole lot of work. It just sits there in the nucleus of our cell guarding our genetic information. The real work is done by RNA. The RNA goes in there, takes copies of a particular gene that might be needed and then goes to that region of the cell where you make proteins. And it's the RNA that oversees the making of the protein. And that work of taking the code from in our cell's nucleus from the DNA and going to make protein, that's called the messenger work of RNA. And that's why these little snippets are called messenger RNAs. And when everybody was trying to race to study the human genome and do the sequencing of DNA, there were some scientists who said, let's look at this more interesting molecule, which, by the way, turns out to be able to replicate itself. And so - lo and behold, it's the beginning of all life on this planet. So RNA turns out to be far more interesting than its brother, DNA.
GROSS: And a recurring theme in your book is that nature is beautiful and that RNA is beautiful. What's beautiful about it?
ISAACSON: RNA is beautiful because it's so simple, which is a four-letter code. It can build any protein that's in our body. It was the molecule that started replicating itself three, 4 billion years ago in this stew that was on our planet. And that's how life begins on our planet. And RNA can serve as a guide to help cut up pieces of DNA, which is what gene-editing technology is all about. Or it could serve as a messenger to say, hey; build this protein in the cell because that mimics a spike protein on a coronavirus. And that way, the person will be immune to coronavirus. And so RNA can do all these things, act as a guide for scissors, act as a messenger to build proteins. And it really does the daily work every, you know, time we need proteins built for anything, whether it's our hormones or our hair or our eyes or the little things that - the neurons in our brain.
GROSS: So CRISPR - spelled C-R-I-S-P-R - is an acronym for a big scientific term that I don't think you even need to mention because no one will understand what it means (laughter). But anyway, so CRISPR is a gene-editing tool. Before we get to how that uses RNA, what does it mean to be a gene-editing tool? What are some of the ways that's being used now?
ISAACSON: If you want to change the genes in our body, you can do it just by snipping them out and sometimes putting in a replacement. So let's say somebody has sickle cell anemia or Huntington's. That's a simple single-gene mutation. And so you can change it with a gene-editing tool. In the future, you might be able to do more complicated things, change hair color, a muscle mass or memory cells in a human being. And so what we do with gene-editing tools is we can fix diseases. And a little bit more controversially, we can edit the embryos of our children and make permanent changes in the human race.
You can
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