Showing posts with label CRISPR. Show all posts
Showing posts with label CRISPR. Show all posts

Tuesday, November 27, 2018

China claims to have created the World’s first designer twins



China’s claim of using gene-editing to create the World’s first designer babies have stirred outrage in the scientific world. The researchers fear that it will stall their efforts to translate gene-editing technology into safe treatments for genetic diseases.

He Jiankui is a Stanford and Rice University-trained physicist and claims to have used CRISPR-Cas9 to delete the embryos’ CCR5 gene (C-C motif chemokine receptor 5), which is linked to resistance to HIV infection and the twins were born a few weeks ago with innate immunity to HIV, the virus that causes AIDS.


He Jiankui

In 2010, when Jiankui was a Rice University student, he already published a paper on details about gene-editing using the bacterial immune system CRISPR. It was well before Geneticist Jennifer Doudna co-invented the groundbreaking current technology for editing genes, called CRISPR-Cas9.

He currently works at the Southern University of Science and Technology of China in Shenzhen and has posted videos to YouTube about his editing techniques. The research is not yet published in a peer-reviewed journal and is, however, yet to be verified by outside scientists and researchers.

The news stunned the scientist and researchers all over the globe as they prepare to gather in Hongkong for the Second International Summit on Human Genome Editing from November 27-29, 2018. David Baltimore, Nobel laureate and chair of the organizing committee said, “I don’t know the details.”

 “We don’t know what will be said,” when He speaks at a session on human embryo editing on Tuesday, November 27, 2018.

There are two main issues with the existing gene-editing technique if used to create ‘designer babies’ in the real world. The first is mosaicism, in which the edited gene does not make it way into every cell of the embryo and second are off-target effects, where other parts of the genome may get deleted accidentally, and the consequences remain unknown.




Before genome editing is used as medical treatment, it is essential that the issues of mosaicism and off-target effects are resolved. Long-term follow-up of babies who have had gene-editing done is needed to know about long-term effects.

It is also unclear that why this particular gene was editing in the twins, but reports coming out of China suggest that the father was HIV positive, but his infection was under control and mother was HIV negative. The scientists also fail to understand that why he chose the HIV gene for editing, as there already exist proven treatments to prevent HIV-positive parents from infecting their children.
There are also specific risks of having a disabled CCR5 gene, which includes a higher risk of West Nile virus infection and dying from Influenza.

The summit’s organizing committee issued a statement Monday saying they had only just learned of He’s research in Shenzhen, China. “Whether the clinical protocols that resulted in the births in China conformed with the guidance” of leading scientific bodies for conducting clinical trials of heritable genome editing “remains to be determined,” the statement said. “We hope that the dialogue at our summit further advances the world’s understanding of the issues surrounding human genome editing. Our goal is to help ensure that human genome editing research is pursued responsibly, for the benefit of all society.”

Meanwhile, Chinese officials have condemned He’s research and strongly oppose the use of gene-editing technology in humans. gene-edited babies are prohibited in China. The Ethical Guiding Principles for the Research of Human Embryonic Stem Cell which was published by the Chinese government in 2003 states that scientists are allowed to conduct genetic editing to human embryos only for research purposes, but the time for their in-vitro breeding shall not exceed 14 days from the date of fertilization or nucleus transplant.

Here is a YouTube video showing He giving information about the twins





Saturday, April 7, 2018

How crisper works? Excellent 2 minutes video about CRISPR technology

courtesy: ISTOCK

CRISPR
 or clustered, regularly interspaced, short palindromic repeat (CRISPR) is a versatile tool for genome engineering used for generating RNA-guided nucleases, such as Cas9, with customizable specificities.

The tool allows scientists to make precise edits to DNA strands, which could lead to treatments for genetic diseases ... but could also be used to create so-called "designer babies."

It has already been used for human trait selection in the UK, as we have seen in the three-parent in vitro fertilization for eliminating mitochondrial diseases.

Here is a beautiful, short two minutes video by STAT, explaining how CRISPR works. 


Sunday, November 12, 2017

Clinical somatic gene editing could be a reality, human enhancement is still a distant shot says the Bioethics committee

https://geneticliteracyproject.org
It is nearly four years ago, scientists reported that clustered regularly interspaced short palindromic repeats-Cas9 (CRISPR-Cas9) technology can enable precise and efficient genome editing in living eukaryotic cells. Since then, scientists are looking for feasibility of successful somatic and germline editing to eliminate many devastating genetic diseases. But, it also comes with a thorny international debate as it opens the door to designer babies and engineered humans.

On August 2, 2017, scientists at the Oregon Health & Science University reported that they had succeeded for the first time in United States in correction of the dominant MYBPC3 mutation that causes a late-onset familial version of hypertrophic cardiomyopathy using CRISPR/Cas9. 


What is DNA editing


One day after this paper was published in Nature, the American Society of Human Genetics (ASHG), and 11 organizations including representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, the International Genetic Epidemiological Society, and the US National Society of Genetic Counselors, as well as the ASHG,  published a joint statement in August concentrating on the prospects for germline alteration. 

The statement as published in the AmericanJournal of Human Genetics, again reiterated that clinical use of germline editing is not allowed at present- these are genetic changes that would be in every cell of a resulting baby and be passed on to future generations, viewed as ‘ethical violation’ by many.  
On the plus side, it provides the only hope for some parents who are carriers of genetic diseases with their best or most acceptable option for having genetically related children who are born free of these diseases. 

Germline somatic editing has already entered clinical trials for non-heritable applications, for treating or preventing diseases or disabilities at this time.

There are three important differences between the two approaches.
1.     Somatic therapies target genes in specific types of cells (lung cells, skin cells, blood cells, etc), while germline modifications, applied to embryos, sperm or eggs, alter the genes in all the resultant person’s cells.
2.      Somatic cell modifications are not biologically transferred to next generations, so it only affects one individual.  Germline editing would be inheritable, have greater impact as it would affect the generations to come.
3.     Clinical trials involving somatic cell therapies are around over two decades now, while human germline editing studies have only just begun this year.

There are a host of unanswered ethical and scientific dilemmas, around the procedure but it does not deny the prospects of germline editing, if the ethical and policy guidelines are met. More stringent regulations would need to be in place, to ensure safety and efficacy when tinkering with human nature

Currently, heritable germline editing is not permissible in the United States.  It is only allowed for purpose of research as the statement published in the American Journal of Human Genetics after 16 months of deliberation, “Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing.”

It suggested that research into genetic modifications should continue as long as it doesn’t lead to a pregnancy.

This ASHG statement is the second set of recommendations issued in 2017, following an exhaustive 300 pages NationalAcademy of Sciences, Engineering, and Medicine (NASEM) document “Human Genome Editing: Science, Ethics, and Governance.” 

The NASEM statement is more wide and covers somatic gene editing, but both the statements expressed reservations currently on using germline editing for creating ‘engineered humans’, but did not deny the possibility of it in future.

Both statements also called for public funding, for manipulating human embryos and fetuses for research, arguing that without funds the research may move offshore, where less stringent regulations and transparency prevails and that may result in rogue experimentation.

Human genome editing is already widely used in basic research and is in the early stages of development and trials for clinical applications that involve non-heritable (somatic) cells.

The Chinese and U.K laws are already in place.

Biologist Paul Knoepfler estimates that genetically modified people will no longer be a science fiction fantasy; it's a likely future scenario. Within fifteen years, scientists could use the gene editing technology CRISPR to make certain "upgrades" to human embryos — from altering physical appearances to eliminating the risk of auto-immune diseases. 

As Victor Hugo said, “there is nothing more powerful than an idea whose time has come.” So, now it’s a question of “when”, instead of “never”.
Here is a video by Françoise Baylis, a philosopher and professor at Dalhousie University, is one of the foremost voices among bioethics scholars worldwide.

Her mission is to foster an inclusive dialogue on what should and should not be allowed through gene editing. As the consequences of these decisions will affect future generations





Saturday, March 18, 2017

Here are the top 5 posts this week.

Ovarian Transposition: A novel laparoscopic surgical method video by Cleveland Clinics.
A recent article published in forthcoming issue of Fertility and Sterility describes and demonstrate novel surgical method of laparoscopic ovarian transposition. This is a minimal invasive approach in which the ovary is tunneled through a peritoneum.

Treating Hypothyroidism and hypothyroxinemia in pregnancy? Clinical dilemma continues.
Treating antenatal patients with levothyroxine who have hypothyroidism or hypothyroxinemia between 8 to 20 weeks of pregnancy did not result in better cognitive outcome and IQ in children through 5 years of age as compared to women who received placebo.
The study was published online on March 2, 2017 in the New England Journal of Medicine.

Vitamin B, a personal weapon to mitigate the effects of Air Pollution.
Vitamin B could attenuate the effects of most dangerous type of air pollution and could be used at personal level to protect against the ill effects. The study was recently published in Proceedings of the National Academy of Sciences of the United States of America.

Wow, new paper based test can tell your blood group in 30 seconds!
Researchers working at the Third Military Medical University in Chongqing, China have developed a quick and reliable test to know the blood type in seconds and rapidly determine the compatibility of donor and recipient blood samples before transfusion.

CRISPR co-inventor Jennifer Doudna keynote address about responsible use of gene editing in future.
“What if a cell’s DNA could be edited just like the text of a document so that you could actually erase letters, you could erase whole sentences, [you could] replace sentences, and you could do things that would enable scientists to change the mutations that might cause genetic disease, make changes that allow us to understand the function of DNA and different kinds of organisms and perhaps, enable us to really direct the way that organisms are evolving on the planet?”
With this promising words about future of CRISPR Cas9 technology Jennifer Doudna, co-inventor of CRISPR Cas9 technology started her keynote address at 2017 South by Southwest (SXSW) conference.


Monday, March 13, 2017

CRISPR co-inventor Jennifer Doudna keynote address about responsible use of gene editing in future.

“What if a cell’s DNA could be edited just like the text of a document so that you could actually erase letters, you could erase whole sentences, [you could] replace sentences, and you could do things that would enable scientists to change the mutations that might cause genetic disease, make changes that allow us to understand the function of DNA and different kinds of organisms and perhaps, enable us to really direct the way that organisms are evolving on the planet?”

With this promising words about future of CRISPR Cas9 technology Jennifer Doudna, co-inventor of CRISPR Cas9 technology started her keynote address at 2017 South by Southwest (SXSW) conference.

The whole invention of CRISPR Cas9 technology is a result of curiosity developed research project aimed at understanding how bacteria fight viruses. It started as adaptive immune system in bacteria that could be harnessed into a powerful gene editing tool that will have profound influence on the world. What started in academic laboratory and is now adopted by clinicians, scientist, government regulatory agencies and commercial companies to develop the technology for human applications for eliminating many genetic diseases.  This is a very young technology ( 5 years )which is evolving very rapidly. 

She further cited many examples where the CRISPR Cas9 technology will find application in animals and plants. It’s application in plants could change the way we look at GMO foods. It can be used to create gene drivers that enable us to drive a trait through population very rapidly. This can be used in near future to create mosquitos that are resistant to infections, thereby limiting the spread of disease.
It will also increase our understanding of why certain genetic traits in a population makes them resistant to develop cancer.

Another application of the Cas9 technology is using it to create animals that are better suited for organ donors.  In principle, we can create organ donor pigs that are better suited for human organ replacement. 

In humans, one of the earliest clinical trials regarding the clinical application of using Cas9 gene editing technology will be to correct the mutation that causes sickle cell disease and is expected to start in couple of years.

Clinical trials are already ongoing in China and USA to make changes in immune system of cancer patients to make their immune cells capable of finding cancer cells  and mounting an immune response in destroying these cells.

All these are somatic applications of the amazing technology, it can also be used for altering the germ cells. Germ line editing application of Crispr technology is surrounded by ethical dilemmas because whatever changes are made will be transferred to coming generations.

It gives us powers to make changes to DNA that will be inherited by future generations. We will be creating traits that we consider enhancement and creating super humans.

Creating Superhumans: From Jennifer Doudna keynote speech.

At present human embryo editing, is only allowed for research purpose till 14 days stage of development and not for clinical use to get pregnant till the ethical and moral considerations are addressed fully across international borders.

She concluded her lecture by iterating her interest of developing this technology further by engaging and educating with public about ethical use of CRISPR for gene editing for treating genetic diseases and not for some sort of harmful effects.

She invited the public to visit the website of Innovative Genomic Institute, a partnership between  UC San Francisco and UC Berkeley which educates the public about coordination between various  institution to go forward with application of this technique in agriculture and responsible use in  human beings. 

Dr. Jennifer Doudna, Ph.D. was named one of Time Magazine’s 100 Most Influential People in 2015.  She is a professor of molecular and cell biology and chemistry at the University of California, Berkeley, where she holds the Li Ka Shing Chancellor’s Chair in Biomedical and Health Sciences and is a Howard Hughes Medical Institute investigator.

Here is the full lecture at the SXSW conference,2017. 









Saturday, November 19, 2016

Cleveland Clinic's Top 10 Medical Innovations for 2016

Cleveland Clinic Innovations hosts the Medical Innovation Summit every Fall to bring together all stakeholders in healthcare industry to advance the conversation of medical innovation. They not only discuss the medical breakthroughs in the current year and but also sketch the blueprint for forthcoming innovations in the coming year.
The stakeholders in the summit includes investors, entrepreneurs, researchers, scientists and government personnel and policy makers that will influence the development and marketing of the new discoveries.
This year the summit was held from October 24-26,2016 at Cleveland, Ohio.
The top ten medical innovations for the year 2016 are:

1)      Vaccines to Prevent Public Health Epidemics.

The top spot in the top ten medical innovation list goes to researchers, scientists and public health personnel who are working tirelessly to develop safe, efficient and effective vaccines to prevent disease epidemics. These efforts were geared up by the 2014 Ebola epidemic in Africa and of bacterial meningococcal (Meningococcal B) outbreaks in the United States. The most promising Ebola vaccines was fast-tracked in less just a year. The researchers incorporated a small fragment of surface protein into a harmless cattle vaccine, which retains its capacity to generate a full blown immune response, but loses its ability to cause disease.  Phase-3 clinical trials in population with full exposure to Ebola virus has shown 100% efficacy in just 10 days.
Similarly, the Meningococcal B vaccine is freely available to all in the year 2016.[1]

2)      Genomic Directed Clinical Trials

Identification of essential tumor growth drivers has initiated a new era of targeted genomic cancer therapy. It gives cancer patients a higher chance of survival, longevity and best chance of cure when they need it most. Patients are waiting too long to enter clinical trials which may decrease their chances of cure or survival. RCT which has long been the gold standard of clinical trials are not keeping in pace with rapid expanding world of gene based and genomic therapy. Genomic based clinical trials can help identify the molecular profile of patient cancer cells and help getting them faster into clinical trials. Those patients with rare type of cancers can also hope for a cure due to genomic trials.

3)       Gene Editing Using CRISPR

CRISPR or clustered, regularly interspaced, short palindromic repeat (CRISPR) is a versatile tool for genome engineering used to generating RNA-guided nucleases, such as Cas9, with customizable specificities. It has many innovative application from treating diseases to editing the genes of human embryos to eliminate many genetic diseases. [2]


4)       Water Purification Systems for Prevention of Infectious Diseases.

Developing countries all over the world are struggling to provide clean drinking water to its majority of population. Sewage often pile up and eventually end up contaminating the drinking water. This contributes to more than 10% of disease in the world
An estimated 700million people in the world are drinking contaminated water
According to the world health organization - more than a million children under the age of five (in developing countries) die each year as a result to contaminated water and poor sanitation [3] LifeStraw has developed a system which transforms sewage into safe drinking water, not for a small group of people but larger communities for extended period of time. The machine collects the waste from the sewage then boils it and collects the condensed water vapor and process it into clean and safe drinking water. One processor is said to generate enough water for 100,000 people.[4]

5)      Cell-Free Fetal DNA Testing

In USA, cell-free DNA analysis became clinically available in 2011 and the American College of Obstetricians and Gynecologists and the Society for Maternal–Fetal Medicine recommended it as a screening option for women at increased risk of fetal aneuploidy. Its use has since been expanded as a screening tool in general obstetric population.Fetal circulating cell free DNA is derived mostly from placenta and is present in maternal blood for testing as early as 10 weeks of gestation. Different laboratories have validated different techniques and mainly rely on next-generation sequencing technologies and advanced bioinformatic analyses.Cell free DNA is commonly used to screen for only the common trisomies and, if requested, sex chromosome composition. The sensitivity and specificity as well as the negative predictive value of the method is >99% for trisomy 21 (Down syndrome), with slightly lower performance for trisomy 13 and 18.

6)      Cancer Screening via Protein Biomarker Analysis

Scientist and researchers have long focused on detection of change in concentration of single protein in biological fluids such as blood or urine to screen for cancer. But, the tests have been of limited use due to low sensitivity and specificity. Currently Studying cancer proteomics holds promise in near future to detect tell-tale proteins that provides insight into biological process of alteration in protein due to cancer. This is very true for detection of prostate cancer and colorectal cancers.

The Lerner Research Institute (LRI) of the Cleveland Clinic maintains the Proteomics Core, a protein-sequencing facility that uses tandem mass spectrometry methods to sequence and identify proteins. [5]
In an Australian study published in PLOS one Fung KYC et al identified three biomarkers that discriminated between the controls and the colorectal cancer patients with 73 percent sensitivity at 95 percent specificity.[6] Similarly tests for prostate cancer showed 100 percent sensitivity with no false negatives and approximately 80 percent specificity.  

7)       Naturally Controlled Artificial Limbs

Numerous innovations in prosthetics over the last decade have improved quality of life for numerous amputees and paraplegics in United States. Researchers have discovered that neural signals for limb movements can be de-coded by computers. This advance was made possible by technologies developed under Defense Advanced Research Projects Agency. Now people living with missing or paralyzed limbs will be able to get a feel of the objects they are touching via prosthesis but also will be able to send signals to the robotic prosthesis device form brain.

“We’ve completed the circuit,” said DARPA program manager Justin Sanchez. “Prosthetic limbs that can be controlled by thoughts are showing great promise, but without feedback from signals traveling back to the brain it can be difficult to achieve the level of control needed to perform precise movements. By wiring a sense of touch from a mechanical hand directly into the brain, this work shows the potential for seamless bio-technological restoration of near-natural function.”[7]

8)      First-ever Treatment For HSDD

The little pink pill or Flibanserin (Addyi, Sprout Pharmaceuticals) also dubbed  as the "Female Viagra" was approved by the US Food and Drug Administration (FDA) for the treatment of  hypoactive sexual desire disorder (HSDD) in premenopausal women,  in August 2015, despite  being unsure  about suboptimal risk-benefit trade-offs.

Flibanserin, a 5-HT1A agonist, a 5-HT2A antagonist, and a very weak partial agonist on dopamine D4 receptors, increases levels of dopamine and norepinephrine and decreases serotonin in animal brain areas. Therefore, since dopamine and norepinephrine are thought to promote and serotonin is thought to inhibit sexual desire and arousal, it was suggested that flibanserin enhances sexual desire in HSDD.

9)      Frictionless Remote Monitoring


Monitoring the blood glucose by pricking the finger will soon be a thing of past.
Wearable  biosensors now measure glucose levels using tissue fluids like tears and sweat and not blood. The WBS transmits data over WiFi to the mobile receiver. The patient hence will be able to continuously monitor his or her glucose level and share the results with healthcare providers. Other frictionless remote monitoring devices in development include a bandage that reads sweat molecules to diagnose pregnancy, hypertension or hydration.[8]

10)  Neurovascular Stent Retriever

Neurovascular stent retrievers are a crucial type of medical equipment used in the treatment of strokes. They are used to clear up intracranial arteries and restore normal blood flow following a stroke. Their rapid action in clearing arteries and retrieving clots in large arteries has been noted by health-care authorities after preliminary trials showed promising results. In June, the American Heart Association and American Stroke Association updated its guidelines and added the use of stent retrievers in conjunction with tPA for first-line treatment in some patients with acute ischemic stroke. The stent retrievers are the Solitaire (Medtronic) or Trevo ProVue (Stryker).





[1] http://innovations.clevelandclinic.org/Summit/Top-10-Medical-Innovations/Top-10-for-2016/1-Vaccines-to-Prevent-Public-Health-Epidemics.aspx
[2] http://www.nature.com/news/crispr-gene-editing-is-just-the-beginning-1.19510
[3] https://prezi.com/crxawgoncdfn/water-purification-systems-for-prevention-of-infectious-dise/
[4] http://www.ippinka.com/blog/lifestraw-water-purification-project-for-millions/
[5] http://journals.lww.com/oncology-times/blog/onlinefirst/Pages/post.aspx?PostID=1352
[6] Fung KYC, Tabor B, Buckley MJ, Priebe IK, Purins L, Pompeia C, et al. (2015) Blood-Based Protein Biomarker Panel for the Detection of Colorectal Cancer. PLoS ONE 10(3): e0120425. doi:10.1371/journal.pone.0120425
[7] http://www.darpa.mil/news-events/2015-09-11
[8] https://www.mepits.com/tutorial/180/Biomedical/Wearable-Biosensors