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Splicing and Dicing DNA: Genome Engineering and the CRISPR Revolution

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Splicing and Dicing DNA: Genome Engineering and the CRISPR Revolution

CRISPR: It’s the powerful gene editing technology transforming biomedical research. Fast, cheap and easy to use, it allows scientists to rewrite the DNA in just about any organism—including humans—with tests on human embryos already underway. The technique’s potential to radically reshape everything from disease prevention to the future of human evolution has driven explosive progress and heated debate. Join the world’s CRISPR pioneers to learn about the enormous possibilities and ethical challenges as we stand on the threshold of a brave new world of manipulating life’s fundamental code.

This program is part of the Big Ideas Series, made possible with support from the John Templeton Foundation.

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Original Program Date: June 3 2016
MODERATOR: Richard Besser
PARTICIPANTS: George Church, Luke Dow, Josephine Johnston, Ben Matthews, Harry Ostrer, Noel Sauer

What is CRISPR? 00:05

Introduction by Richard Besser 3:58

Participant Introductions. 5:02

What is so powerful about CRISPR? 7:25

How is CRISPR is used? 13:00

How will CRISPR help eliminate Zika Virus? 20:45

Modifying 60 genes at once in a pig. 26:02

What are potential agricultural advantages from CRISPR? 28:44

If you have eaten CRISPR cells? 35:00

Using a gene drives to eliminate virus? 37:40

Creating an off switch for CRISPR 40:27

How is it ethical to not rid the world of malaria? 42:55

What is the difference between editing a germ line and editing a cancer cell? 48:27

Why would the first CRISPR baby create backlash? 58:48

How do we regular CRISPR used in military applications? 1:06:33

What is the regulation to be expected from CRISPR? 1:13:09

What does a CRISPR-ised world look like? 1:16:00
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Splicing and Dicing DNA: Genome Engineering and the CRISPR Revolution

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CRISPR in Context: The New World of Human Genetic Engineering

It’s happened. The first children genetically engineered with the powerful DNA-editing tool called CRISPR-Cas9 have been born to a woman in China. Their altered genes will be passed to their children, and their children’s children. Join CRISPR’s co-discoverer, microbiologist Jennifer Doudna, as we explore the perils and the promise of this powerful technology. It is not the first time human ingenuity has created something capable of doing us great good and great harm. Are we up to the challenge of guiding how CRISPR will shape the future?

PARTICIPANTS: Jennifer Doudna, Jamie Metzl, William Hurlbut

MODERATOR: Guy McKhann

MORE INFO ABOUT THE PROGRAM AND
PARTICIPANTS:

TOPICS
0:00 - Introduction
1:55 - Jennifer Doudna introduction
2:25 - How do we learn to use CRISPR technology wisely?
3:29 - The basics of understanding CRISPR
6:04 - Genetic engineering explainer film
7:39 - How can CRISPR help the worldwide food chain?
9:57 - Genetic disease treatment
14:25 - Improving quality of life
15:55 - Designer babies
17:55 - The gene drive
19:25 - Confronting the ethical implications of CRISPR
23:55 - Jennifer’s childhood in Hawaii
28:25 - Patents
32:08 - Importance of accuracy
32:40 - Germ cells vs somatic cells
35:58 - He Jiankui controversy
40:05 - What makes CRISPR dangerous?
43:48 - How do we enforce regulation of CRISPR use?
53:50 - The aftermath of He Jiankui’s work
1:09:25 - How do we make CRISPR technology accessible globally?
1:14:00 - How do we balance natural biology and CRISPR?
1:18:44 - How will CRISPR impact our future as a species?

PROGRAM CREDITS
- Produced by Nils Kongshaug
- Associate Produced by Emmalina Glinskis
- Music provided by APM
- Additional images and footage provided by: Getty Images, Shutterstock, Videoblocks.
- Recorded at the Simons Foundation's Gerald D. Fishbaum Auditorium

The Kavli Prize recognizes scientists for their seminal advances in astrophysics, nanoscience, and neuroscience. The series, “The Big, the Small, and the Complex,” is sponsored by The Kavli Foundation.

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What is CRISPR & How Could It Edit Your DNA?

Gene-editing tool CRISPR is everywhere in the news, but what is it and could it eliminate disease?

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Should We Make Designer Babies? ►►►►

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CRISPR: A game-changing genetic engineering technique

Have you heard? A revolution has seized the scientific community. Within only a few years, research labs worldwide have adopted a new technology that facilitates making specific changes in the DNA of humans, other animals, and plants.

CRISPR gene therapy: Scientists call for more public debate around breakthrough technique

The technique, known as CRISPR, could revolutionise human gene therapy and genetic engineering because it allows scientists for the first time to make the finest changes to the DNA of the chromosomes with relative ease.
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CRISPR Science: DNA, RNA, and Gene Editing

This video provides a quick refresher on DNA before introducing gene-editing. In five minutes you get both a lesson on DNA and CRISPR, which is pronounced crisp-er. If you already know the basics of DNA you can jump to the CRISPR section at 3:22. To learn more about this tool you can visit the companion story on Ask A Biologist -

3. Genetic Engineering

Frontiers of Biomedical Engineering (BENG 100)

Professor Saltzman introduces the elements of molecular structure of DNA such as backbone, base composition, base pairing, and directionality of nucleic acids. He describes the processes of DNA synthesis, transcription, RNA splicing, translation, and post-translational processing required to make a protein such as insulin from its genetic code (DNA). Professor Saltzman describes the genetic code. RNA interference is also discussed as a way to control gene expression, which can be applied as a new way to treat diseases.

00:00 - Chapter 1. Introduction
01:35 - Chapter 2. Building Blocks of DNA
11:17 - Chapter 3. Structure of DNA and RNA
24:16 - Chapter 4. Central Dogma and DNA Synthesis
35:15 - Chapter 5. Genetic Code and Protein Synthesis
41:55 - Chapter 6. Control of Gene Expression

Complete course materials are available at the Open Yale Courses website:

This course was recorded in Spring 2008.

What is CRISPR? Jennifer Doudna on cutting and pasting DNA

2015 Breakthrough Prize laureate Jennifer Doudna talks about the medical promise and ethical challenges of the CRISPR-Cas9 gene-editing technology.

Genetically Modified Humans? CRISPR/Cas 9 Explained

This week Reactions dives into your DNA with the science and chemistry behind CRISPR/Cas 9. Fans of Blade Runner have already caught a glimpse of world with super-powered humans secretly living among us, capable of physical feats far beyond your everyday person. But now, with the the CRISPR/CAS9 Gene editing system, are we looking at a future with real replicants? Check out this video to get an inside look at how CRISPR works, and the sorts of wild medical advances that are on the horizon.

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CHECK OUT ACS CENTRAL SCIENCE!


Producer: Kirk Zamieroski

Writers: Megan Cartwright & Kirk Zamieroski

Executive Producer:
Adam Dylewski

Scientific consultants:
Chase Biesel, Ph.D
Martin Jinek, Ph.D.
Kyle Nackers

Music:
Roberto Daglio - Mr. Fantastic
Sam Leopard - Back for More

Sources:

Video interviews with Jennifer Doudna:






Notes from CRISPR talk by Françoise Baylis at AAAS:

Addgene. CRISPR/Cas9 Guide. Web:

Addison et al. 2015. Gene Editing and Germ-line Intervention: The Need for Novel Responses to Novel Technologies. Molecular Therapy. Web:

Barrangou et al. 2007. CRISPR Provides Acquired Resistance Against Viruses in Prokaryotes. Science. Web:

BBC. 1 February 2016. Scientists get 'gene editing' go-ahead. Web:

Chen et al. 2015. Functional disruption of the dystrophin gene in rhesus monkey using CRISPR/Cas9. Human Molecular Genetics. Web:

Deltcheva et al. 2011. CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature. Web:

Guo et al. 2015. Targeted genome editing in primate embryos. Cell Research. Web:

Jansen et al. 2002. Identification of genes that are associated with DNA repeats in prokaryotes. Molecular Microbiology. Web:

Jinek et al. 2012. A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity. Science. Web:

Komor et al. 2016. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature. Web:

Liang et al. 2015. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein & Cell. Web:

MIT Technology Review. 11 February 2014. Genome Surgery. Web:

MIT Technology Review. 5 March 2015. Engineering the Perfect Baby. Web:

Nature. 1 April 2015. Mini enzyme moves gene editing closer to the clinic. Web:

Nature. 29 September 2015. Gene-edited 'micropigs' to be sold as pets at Chinese institute. Web:

Nature. CRISPR, the disruptor. 3 June 2015. Web:

Science. 17 December 2015. And Science’s 2015 Breakthrough of the Year is... Web:

The Verge. 20 April 2016. Breakthrough method means CRISPR just got a lot more relevant to human health. Web:

Melissa L. Hefferin, Alan E. Tomkinson, Mechanism of DNA double-strand break repair by non-homologous end joining, DNA Repair, Volume 4, Issue 6, 8 June 2005, Pages 639-648, ISSN 1568-7864,


Ever wonder why dogs sniff each others' butts? Or how Adderall works? Or whether it's OK to pee in the pool? We've got you covered: Reactions a web series about the chemistry that surrounds you every day.

Reactions is produced by the American Chemical Society.

Meet the biohacker using CRISPR to teach everyone gene editing

Meet the biohacker who wants to teach everyone how to edit genes

Josiah Zayner is a biohacker who thinks everyone should be able to change their DNA with biotechnology called CRISPR. That’s why he founded a company called The ODIN, which sells do-it-yourself biotech kits that teach people how to genetically modify bacteria and frogs. It's DIY gene therapy.

His company has sold tens of thousands of experiments using CRISPR, an inexpensive and precise gene-editing technology that has revolutionized the field.

Find more on CRISPR at Quartz

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Quartz is a digital news outlet dedicated to telling stories at the intersection of the important and the interesting. Visit us at to read more.

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The Long & Short of It: The Genome Revolution

The genome medicine revolution is front and center as advancements in scientific knowledge and falling costs have raised the possibility of curative treatments for afflictions like blindness and cancer, according to Salveen Richter of Goldman Sachs Research. Learn More
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DNA Science - Human Race and Genetics Documentary

Genetically modified dogs: Chinese scientists use CRISPR to create muscly freaks - TomoNews

GUANGZHOU, CHINA — Scientists of the Key Laboratory of Regenerative Biology at the Guangzhou Institutes of Biomedicine and Health claim to be the first to use genome modification to double the muscle mass of dogs.

Their findings, recently published in the latest edition of the Journal of Molecular Cell Biology, have broken new ground in the field of genetic engineering. For this new research, the scientists used 65 beagle dog embryos, focusing in on genes encoded for myostatin, a protein that inhibits muscle growth. By injecting the enzyme complex CRISPR-Cas9 into the embryos, the objective was to knock out the myostatin genes in the DNA of the canines. With myostatin deleted, the beagles would be able to reach new levels of muscle growth.

The breakthrough study resulted in the births of 27 beagle puppies. The scientists report only two of them, a boy they named Hercules and a girl they named Tiangou, had disruptions in their myostatin genes. The researchers say that the gene editing turned out to be incomplete in Hercules, allowing for a percentage of his muscle cells to continue to produce myostatin. But with Tiangou, the gene editing was indeed complete, resulting in her thigh muscles growing to be significantly larger than those of her litter mates. The scientists say the dogs have more muscles and are expected to have stronger running ability, which could make for freakishly powerful hunting dogs and military canines.

In the past, the Chinese have performed gene editing on goats, rabbits, rats, monkeys and even human embryos. While the scientists say this particular study was undertaken to learn more about gene modification for human disease treatments, such as Parkinson’s and muscular dystrophy, it’s hard not to wonder what else they might do.

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The Realities of Gene Editing with CRISPR I NOVA I PBS

CRISPR gene-editing technology is advancing quickly. What can it do now—and in the future?

The revolutionary gene-editing tool known as CRISPR can alter, add, and remove genes from the human genome. The implications are immense: It could help eliminate illnesses like sickle cell disease and muscular dystrophy, and could even allow us to alter the genes of future generations of humans, leading to so-called designer babies. But will this ever really happen?

Medical journalist and pediatrician Alok Patel investigates the current state of CRISPR—starting with a bull calf named Cosmo. Patel discovers how scientists edited Cosmo’s genome so he would produce more male offspring, and what that means for humans. In conversation with scientists, artists, and ethicists, Patel explores what kind of gene editing is actually possible right now—and what we should be thinking about when we consider manipulating human traits and, ultimately, the human experience.

PRODUCTION CREDITS:

Hosted by Dr. Alok Patel

WRITTEN, PRODUCED AND DIRECTED BY
Caitlin Saks

EDITED BY
Robert Kirwan

ASSISTANT EDITOR
Jay Colamaria

CAMERA
Arlo Pérez

UC DAVIS FIELD DIRECTOR / CAMERA
Zachary Fink

ASSOCIATE PRODUCERS
Ana Aceves
Christina Monnen
Arlo Pérez
Jay Colamaria

PRODUCTION ASSISTANT
Lorena Lyon

INTERNS
Jessie Hendricks
Samuel Lipsey

AMERICAN SIGN LANGUAGE / ENGLISH INTERPRETER
Adam Bartley

ANIMATION
Edgeworx Studios

ADDITIONAL ANIMATION
2K-12 Studios
Mitch Butler

MUSIC
APM

ONLINE EDITOR AND COLORIST
David Bigelow

AUDIO MIX
Chris Anderson

ARCHIVAL MATERIAL
AP Archive
Broad Institute of MIT and Harvard
Getty Images
He Jiankui Lab / CC BY
Penn Medicine
Pond 5
Storyblocks

SPECIAL THANKS
Mike Baylis -- Assisted in the set up of a remote interview, at no cost.
Isaac Plant -- Reviewed script and graphics for scientific accuracy, at no cost.
Elizabeth Delgado -- Reviewed script and graphics for scientific accuracy, at no cost.
Dr. Samira Kiani -- Reviewed script and graphics for scientific accuracy, at no cost.
Dr. Kim Thornton -- Interviewed but did not include in the final film, at no cost.

Participants:
Françoise Baylis
Teresa Blankmeyer Burke
Karmella Haynes
Xavier LaPlante
David Liu
Bret McNabb
Liana Novoa
Alok Patel
Ariana Pelaez
Brianna Sapienza
Niaz Uddin
Alison Van Eenennaam

Image credit: (DNA helix)

© WGBH Educational Foundation

What is CRISPR? Animation.

How CRISPR/Cas-9 System Works. Why CRISPR is UNLIKE any other DNA editing tools ever discovered? The future of genetic engineering. This video is available for instant download licensing here :
Voice by: Sue Stern
©Alila Medical Media. All rights reserved.
Support us on Patreon and get FREE downloads and other great rewards: patreon.com/AlilaMedicalMedia
CRISPR is the newly discovered revolutionary tool that would allow scientists to change at will any DNA sequence of, presumably, any living organism in a precise manner. Unlike any other previously developed techniques of gene editing, CRISPR is REMARKABLY simpler, faster and cheaper.
CRISPR is part of a naturally occurring defense mechanism found in many bacteria. The bacteria use CRISPR to SPECIFICALLY snip the DNA of invading viruses. CRISPR stands for “Clustered Regularly Interspaced Short Palindromic Repeats” - a region of bacterial genome that contains short DNA repeats with unique sequences, or spacers, in between. These spacers are derived from DNA of viruses that prey on the bacteria. The CRISPR region is essentially a DNA library of all enemies that need to be RECOGNIZED and destroyed. After being transcribed, individual pieces of spacer RNAs form complexes with a protein named Cas, for CRISPR-ASsociated protein. Cas is an endonuclease – an enzyme that cuts DNA. These RNA/protein complexes then drift through the cell, looking for matching viral DNA. If a match is encountered, the RNA latches on, base-paring with it; Cas protein then cuts the viral DNA, disabling the virus.
Scientists have isolated this system, and by designing their own spacer-RNAs, they can, in theory, target any DNA sequences in any organism. The system has indeed worked in all organisms tested so far. The current CRISPR system consists of two components: a guide RNA and a Cas protein named Cas9. The guide RNA is a short synthetic RNA composed of a “scaffold” sequence necessary for Cas9-binding and a user-defined “spacer”, or “targeting” sequence of about 20 nucleotides long.
Applications of the CRISPR system:
- Disabling, or knock-out, a particular gene: After Cas-9 cuts the DNA, the cell would try to repair the break. The more efficient repair pathway in the cell is ERROR-PRONE and would most likely result in a loss-of-function mutation in the gene of interest. As CRISPR modifies BOTH copies of the gene at the same time, generation of knock-out animals and cell lines for gene function studies has never been more efficient. Moreover, MULTIPLE genes can be targeted in one manipulation, making this technique an extraordinarily powerful tool for studying complex genetic traits or diseases that involve many genes.
- Introducing precise modifications to the target DNA: If a desired DNA sequence is provided together with the CRISPR/Cas-9 system, it can be used by ANOTHER repair pathway as a TEMPLATE to reconstruct the disrupted gene sequence. The desired changes stay permanently and are also transmitted to future generations.
- Modifications to the Cas9 enzyme have extended the application of CRISPR to selectively turn ON and OFF target genes, fine-tune their expression WITHOUT permanently altering the gene sequence.
Since its discovery, CRISPR technology has been used extensively in animal research to engineer disease-resistant livestock; bring back extinct species; introduce deleterious genes into malaria-carrying mosquitoes; and modify pig genome to make pig’s organs suitable for transplant into human. CRISPR has also been employed to create “custom designed” pets such as mini-pigs with customized coat patterns, colorful koi fish and dogs with certain desirable traits. The CRISPR zoo is growing rapidly but so are the ethical concerns and fears of possible ecological disasters.
In human, while CRISPR is proven to be a powerful tool to study various diseases, it is deemed NOT YET ready for clinical applications. Modification of human germlines to alter genetic heritage of future generations may also lead to unwanted consequences and is prohibited by most countries.

ABC Catalyst: CRISPR 30 Aug 2016

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CRISPR: The Revolution in Genetics

CRISPR is a revolutionary new technique that allows scientists to precisely edit the activity of genes and thus influence the characteristics of all manner of organisms, from microscopic bacteria to humans. Should we use this technology to prevent harmful diseases in humans being passed on between generations? And should we go even further and use it to enhance our offspring, making them fitter, healthier and more intelligent?

In the last episode of this series of the Life Science Broadcast, zoology professor Matthew Cobb and renowned bioethicist John Harris discuss the applications of CRISPR technology and just how far we should go in using it to change our genomes.

Filmed and produced by Edward Bains, The University of Manchester.

curing disease using genetic engineering.

15 year old talking about curing disease using genetic engineering.

Genetics Crash Course | A Complete Guide to Genetics

IntroBooks is an online learning platform. It brings to you insightful and educational information in the form of articles, ebooks, audiobooks and videos. We invest a lot of time and effort in creating well-researched videos to provide a wealth of information for anyone who yearns for knowledge.

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Genetic gone through a breakthrough in the discovery that DNA would be the fundamental structure carrying the genetic information. Among the various work with this molecule, he stood out to Watson, Crick, Wilkins, and Franklin in 1953, which demonstrated the structure of the DNA double helix.

Using CRISPR Cas9 to cure sickle cell disease

A team of physicians and laboratory scientists has taken a key step toward a cure for sickle cell disease, using CRISPR-Cas9 gene editing to fix the mutated gene responsible for the disease in stem cells from the blood of affected patients.

For the first time, they have corrected the mutation in a proportion of stem cells that is high enough to produce a substantial benefit in sickle cell patients.

The researchers from the University of California, Berkeley, UC San Francisco Benioff Children’s Hospital Oakland Research Institute (CHORI) and the University of Utah School of Medicine hope to re-infuse patients with the edited stem cells and alleviate symptoms of the disease, which primarily afflicts those of African descent and leads to anemia, painful blood blockages and early death.

“We’re very excited about the promise of this technology,” said Jacob Corn, a senior author on the study and scientific director of the Innovative Genomics Initiative at UC Berkeley. “There is still a lot of work to be done before this approach might be used in the clinic, but we’re hopeful that it will pave the way for new kinds of treatment for patients with sickle cell disease.”

In tests in mice, the genetically engineered stem cells stuck around for at least four months after transplantation, an important benchmark to ensure that any potential therapy would be lasting.

“This is an important advance because for the first time we show a level of correction in stem cells that should be sufficient for a clinical benefit in persons with sickle cell anemia,” said co-author Mark Walters, a pediatric hematologist and oncologist and director of UCSF Benioff Oakland’s Blood and Marrow Transplantation Program.

Sickle cell disease is a recessive genetic disorder caused by a single mutation in both copies of a gene coding for beta-globin, a protein that forms part of the oxygen-carrying molecule hemoglobin. This homozygous defect causes hemoglobin molecules to stick together, deforming red blood cells into a characteristic “sickle” shape. These misshapen cells get stuck in blood vessels, causing blockages, anemia, pain, organ failure and significantly shortened lifespan. Sickle cell disease is particularly prevalent in African Americans and the sub-Saharan African population, affecting hundreds of thousands of people worldwide.

The goal of the multi-institutional team is to develop genome engineering-based methods for correcting the disease-causing mutation in each patient’s own stem cells to ensure that new red blood cells are healthy.

The team used CRISPR-Cas9 to correct the disease-causing mutation in hematopoietic stem cells – precursor cells that mature into red blood cells – isolated from whole blood of sickle cell patients. The corrected cells produced healthy hemoglobin, which mutated cells do not make at all. (cont'd)

For the full story:

Video by Roxanne Makasdjian and Stephen McNally





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