Image Caption: Beating-heart cells derived from iPS cells are shown. A single DNA base-pair of the PRKAG2 gene was edited using the method developed by Drs. Miyaoka and Conklin. Credit: Luke Judge/Gladstone Institutes
Anne D. Holden, PhD Gladstone Institutes
Gladstones innovative technique in stem cells to boost scientists ability to study and potentially cure genetic disease
Sometimes biology is cruel. Sometimes simply a one-letter change in the human genetic code is the difference between health and a deadly disease. But even though doctors and scientists have long studied disorders caused by these tiny changes, replicating them to study in human stem cells has proven challenging. But now, scientists at the Gladstone Institutes have found a way to efficiently edit the human genome one letter at a time not only boosting researchers ability to model human disease, but also paving the way for therapies that cure disease by fixing these so-called bugs in a patients genetic code.
Led by Gladstone Investigator Bruce Conklin, MD, the research team describes in the latest issue of Nature Methods how they have solved one of science and medicines most pressing problems: how to efficiently and accurately capture rare genetic mutations that cause disease as well as how to fix them. This pioneering technique highlights the type of out-of-the-box thinking that is often critical for scientific success.
Advances in human genetics have led to the discovery of hundreds of genetic changes linked to disease, but until now weve lacked an efficient means of studying them, explained Dr. Conklin. To meet this challenge, we must have the capability to engineer the human genome, one letter at a time, with tools that are efficient, robust and accurate. And the method that we outline in our study does just that.
One of the major challenges preventing researchers from efficiently generating and studying these genetic diseases is that they can exist at frequencies as low as 1%, making the task of finding and studying them labor-intensive.
For our method to work, we needed to find a way to efficiently identify a single mutation among hundreds of normal, healthy cells, explained Gladstone Research Scientist Yuichiro Miyaoka, PhD, the papers lead author. So we designed a special fluorescent probe that would distinguish the mutated sequence from the original sequences. We were then able to sort through both sets of sequences and detect mutant cellseven when they made up as little one in every thousand cells. This is a level of sensitivity more than one hundred times greater than traditional methods.
The team then applied these new methods to induced pluripotent stem cells, or iPS cells. These cells, derived from the skin cells of human patients, have the same genetic makeup including any potential disease-causing mutations as the patient. In this case, the research team first used a highly advanced gene-editing technique called TALENs to introduce a specific mutation into the genome. Some gene-editing techniques, while effective at modifying the genetic code, involve the use of genetic markers that then leave a scar on the newly edited genome. These scars can then affect subsequent generations of cells, complicating future analysis. Although TALENs, and other similarly advanced tools, are able to make a clean, scarless single letter edits, these edits are very rare, so that new technique from the Conklin lab is needed.
Our method provides a novel way to capture and amplify specific mutations that are normally exceedingly rare, said Dr. Conklin. Our high-efficiency, high-fidelity method could very well be the basis for the next phase of human genetics research.
Original post:
Engineering The Human Genome One Letter At A Time
- Who are We? - November 7th, 2009 [November 7th, 2009]
- Vilsack targeted for his Pro-GMOs stand - November 7th, 2009 [November 7th, 2009]
- Call for technology to produce cellulosic ethanol - November 7th, 2009 [November 7th, 2009]
- Kenyan scientists weigh on GMOs - November 7th, 2009 [November 7th, 2009]
- Indian researcher makes a case for biotechnology - November 7th, 2009 [November 7th, 2009]
- Michigan smoothens the way for alternative energy investors - November 7th, 2009 [November 7th, 2009]
- Link of ethanol use to high food prices questioned - November 7th, 2009 [November 7th, 2009]
- EU challenges France on GM Maize - November 7th, 2009 [November 7th, 2009]
- POET rolls out cellulosic ethanol plant - November 7th, 2009 [November 7th, 2009]
- There’s a bright future for cellulosic ethanol investment - November 7th, 2009 [November 7th, 2009]
- Cellulosic ethanol can considerably reduce gasoline use by 2030 - November 7th, 2009 [November 7th, 2009]
- Human Genetic Engineering - Background - November 7th, 2009 [November 7th, 2009]
- Human Genetic Engineering - History - November 7th, 2009 [November 7th, 2009]
- Human Genetic Engineering - Methods - November 7th, 2009 [November 7th, 2009]
- Human Genetic Engineering - Uses - November 7th, 2009 [November 7th, 2009]
- Human Genetic Engineering - Controversy - November 7th, 2009 [November 7th, 2009]
- Human Genetic Engineering - In popular culture - November 7th, 2009 [November 7th, 2009]
- Human genetic engineering - An Introduction - November 7th, 2009 [November 7th, 2009]
- Human Genetic Engineering - A Very Hot Issue! - November 7th, 2009 [November 7th, 2009]
- What are the risks of genetic engineering in humans? (human genetic engineering) - November 7th, 2009 [November 7th, 2009]
- What are the benefits of human genetic engineering? (human genetic engineering) - November 7th, 2009 [November 7th, 2009]
- Genetic Engineering - Ethics and Controversy - November 7th, 2009 [November 7th, 2009]
- Genetic Engineering Ethics In Science Fiction - November 7th, 2009 [November 7th, 2009]
- Genetic Engineering Ethics - November 7th, 2009 [November 7th, 2009]
- Welcome to Pest Control Exterminator Network - December 13th, 2009 [December 13th, 2009]
- OMD - Genetic Engineering - August 27th, 2011 [August 27th, 2011]
- X-Ray Spex - Genetic Engineering - August 27th, 2011 [August 27th, 2011]
- Ancient Alien Nephilim, Giants, Mutants, Genetic Engineering, and Hybrids (2-6) - August 28th, 2011 [August 28th, 2011]
- Human-Plant Hybrid (Genetic Engineering at Home) - August 28th, 2011 [August 28th, 2011]
- Ancient Alien Nephilim, Giants, Mutants, Genetic Engineering, and Hybrids (1-6) - August 29th, 2011 [August 29th, 2011]
- 3. Genetic Engineering - August 29th, 2011 [August 29th, 2011]
- Genetic engineering nightmare - August 31st, 2011 [August 31st, 2011]
- Ancient Alien Nephilim, Giants, Mutants, Genetic Engineering, and Hybrids (3-6) - August 31st, 2011 [August 31st, 2011]
- Future of genetic engineering - by Futurist Dr Patrick Dixon. Genetic mutations and genetic disorders. Gene science by conference keynote speaker - September 2nd, 2011 [September 2nd, 2011]
- Genetic engineering: The world's greatest scam? - September 3rd, 2011 [September 3rd, 2011]
- Watch Fed Up! Genetic Engineering, Industrial Agriculture and Sustainable Alternatives Full Movie Online Part 1/15 - September 3rd, 2011 [September 3rd, 2011]
- Ancient Alien Nephilim, Giants, Mutants, Genetic Engineering, and Hybrids (5-6) - September 5th, 2011 [September 5th, 2011]
- Genetic Engineering, Humans with Animals. - September 6th, 2011 [September 6th, 2011]
- Is Genetic Engineering Good for the Environment? - September 7th, 2011 [September 7th, 2011]
- Open Source Food and Genetic Engineering - Michael Pollan - September 10th, 2011 [September 10th, 2011]
- Ancient Alien ( demons ) Nephilim Giants, Mutants Genetic Engineering and Hybrids.avi - September 11th, 2011 [September 11th, 2011]
- MUST SEE : Genetic Engineering Corn Grows in Sand ! For Those That Appreciate Nature ! - September 12th, 2011 [September 12th, 2011]
- Designing Humanity - Genetic Engineering - September 14th, 2011 [September 14th, 2011]
- Genetic Modification | QUEEN ANNE SCIENCE CAFE - September 14th, 2011 [September 14th, 2011]
- Genetic Engineering in California Agriculture - September 15th, 2011 [September 15th, 2011]
- Genetic Engineering Animation - September 15th, 2011 [September 15th, 2011]
- Proof Of Ancient Genetic Engineering - September 15th, 2011 [September 15th, 2011]
- Joad Cressbeckler Fears Genetic Modification Causes 'Wrath-Minded Taters' - September 16th, 2011 [September 16th, 2011]
- Ethical Concerns With Genetic Engineering - September 16th, 2011 [September 16th, 2011]
- Scientists under Attack - Genetic Engineering in the magnetic Field of Money TRAILER - September 17th, 2011 [September 17th, 2011]
- Genetic Modification - September 18th, 2011 [September 18th, 2011]
- Genetic Engineering Not a New Science - Pamela Ronald - September 23rd, 2011 [September 23rd, 2011]
- The Island of Dr. Moreau prt. IV - September 28th, 2011 [September 28th, 2011]
- Ancient Alien Nephilim, Giants, Mutants, Genetic Engineering, and Hybrids (4-6) - September 30th, 2011 [September 30th, 2011]
- 4. Genetic Engineering (cont.) - October 2nd, 2011 [October 2nd, 2011]
- Ancient Alien Nephilim, Giants, Mutants, Genetic Engineering, and Hybrids (6-6) - October 4th, 2011 [October 4th, 2011]
- Islands at Risk (Part 3) - Genetic Engineering in Hawai'i - October 4th, 2011 [October 4th, 2011]
- Morgellons Is Genetic Engineering , A Silent Superbug - October 4th, 2011 [October 4th, 2011]
- Islands at Risk (Part 2) - Genetic Engineering in Hawai'i - October 4th, 2011 [October 4th, 2011]
- The Ethics of Genetically Engineering Children - Arthur Caplan - October 4th, 2011 [October 4th, 2011]
- Disney Geneticists Debut New Child Stars - October 4th, 2011 [October 4th, 2011]
- Genetic Engineering and Society, Lecture 1a, Honors Collegium 70A, UCLA - October 4th, 2011 [October 4th, 2011]
- OMD - Genetic Engineering (312mm Version) (Audio Only) - October 4th, 2011 [October 4th, 2011]
- The difference between normal and genetically modified food - October 4th, 2011 [October 4th, 2011]
- Bioethics Of Human Genetic Engineering - Documentary Video - October 6th, 2011 [October 6th, 2011]
- Islands at Risk (Part 1) - Genetic Engineering in Hawai'i - October 6th, 2011 [October 6th, 2011]
- Coast To Coast AM: Genetic Engineering 3-24-2011 Download Link - October 6th, 2011 [October 6th, 2011]
- Lloyd Pye - Ancient Genetic Engineering - October 13th, 2011 [October 13th, 2011]
- X RAY SPEX - ROUNDHOUSE LONDON GENETIC ENGINEERING - Video - October 13th, 2011 [October 13th, 2011]
- OMD - Genetic Engineering 1983 - Video - October 14th, 2011 [October 14th, 2011]
- OMD - GENETIC ENGINEERING - Video - October 14th, 2011 [October 14th, 2011]
- Mechanism of Recombination - Video - October 15th, 2011 [October 15th, 2011]
- Harvard Prof. Michael Sandel on Human Genetic Modification, Berkeley, CA, 7 May 2007 - Video - October 15th, 2011 [October 15th, 2011]
- Genetic Engineering [Medical Ethics Series] - (excerpt) - Video - October 15th, 2011 [October 15th, 2011]
- Genetic Engineering and Society, Lecture 1b, Honors Collegium 70A, UCLA - Video - October 24th, 2011 [October 24th, 2011]
- Genomics: genetic modification (genetic engineering) and the human gene project - Video - October 26th, 2011 [October 26th, 2011]
- Genetically Engineering Intelligent Babies - Horizon: Are We Still Evolving? Preview - BBC Two - Video - October 27th, 2011 [October 27th, 2011]
- "GENETIC ENGINEERING" GERMAN REGIME feat THIRSTIN HOWL THE3RD - Video - October 28th, 2011 [October 28th, 2011]
- Science 360: Genetic Engineering - Video - October 31st, 2011 [October 31st, 2011]
- UFOTV Presents... - Bad Seed: Danger of Genetically Modified Food - Video - November 8th, 2011 [November 8th, 2011]