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Posts Tagged ‘human genome’


CRISPR cuts turn gels into biological watchdogs

Reporter: Irina Robu, PhD

Genome editing if of significant interest in the prevention and treatment of human diseases including single-gene disorders such as cystic fibrosis, hemophilia and sickle cell disease. It also shows great promise for the prevention and treatment of diseases such as cancer, heart disease, mental illness and human immunodeficiency virus infection. However, ethical concerns arise when genome editing, using technologies such as CRISPR-Cas9 is used to alter human genomes.

James Collins, bioengineer at MIT and his team worked with water-filled polymers that are held together by strands of DNA, known as DNA hydrogels. To alter the properties of these materials, these scientists turned to a form of CRISPR that uses a DNA-snipping enzyme called Cas12a, which can be programed to recognize a specific DNA sequence. The enzyme then cuts its target DNA strand, then severs single strands of DNA nearby. This property lets scientists to build a series of CRISPR-controlled hydrogels encapsulating a target DNA sequence and single strands of DNA, which break up after Cas12a identifies the target sequence in a stimulus. The break-up of the single DNA strands activates the hydrogels to change shape or completely dissolve, releasing a payload.

According to Collins and his team, the programmed hydrogels will release enzymes, small molecules and human cells as part of a smart therapy in response to stimuli. However, in order to make it a smart therapeutic, the researchers in collaboration with Dan Luo, bioengineer at Cornell University placed the CRISPR- controlled hydrogels into electric circuits. The circuit is switched off in response to the detection of the genetic material of harmful pathogens such as Ebola virus and methicillin-resistant Staphylococcus aureus. The team used these hydrogels to develop a prototype diagnostic tool that sends a wireless signal to identify Ebola in lab samples.

Yet, it is evident that these CRISPR-controlled hydrogels show great potential for the prevention and treatment of diseases.

SOURCE

https://www.nature.com/articles/d41586-019-02542-3?utm_source=Nature+Briefing

 

 

 

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Reporter and Curator: Irina Robu, PhD

Monitoring cancer patients and evaluating their response to treatment can sometimes involve invasive procedures, including surgery.

The liquid biopsies have become something of a Holy Grail in cancer treatment among physicians, researchers and companies gambling big on the technology. Liquid biopsies, unlike traditional biopsies involving invasive surgery — rely on an ordinary blood draw. Developments in sequencing the human genome, permitting researchers to detect genetic mutations of cancers, have made the tests conceivable. Some 38 companies in the US alone are working on liquid biopsies by trying to analyze blood for fragments of DNA shed by dying tumor cells.

Premature research on the liquid biopsy has concentrated profoundly on patients with later-stage cancers who have suffered treatments, including chemotherapy, radiation, surgery, immunotherapy or drugs that target molecules involved in the growth, progression and spread of cancer. For cancer patients undergoing treatment, liquid biopsies could spare them some of the painful, expensive and risky tissue tumor biopsies and reduce reliance on CT scans. The tests can rapidly evaluate the efficacy of surgery or other treatment, while old-style biopsies and CT scans can still remain inconclusive as a result of scar tissue near the tumor site.

As recently as a few years ago, the liquid biopsies were hardly used except in research. At the moment, thousands of the tests are being used in clinical practices in the United States and abroad, including at the M.D. Anderson Cancer Center in Houston; the University of California, San Diego; the University of California, San Francisco; the Duke Cancer Institute and several other cancer centers.

With patients for whom physicians cannot get a tissue biopsy, the liquid biopsy could prove a safe and effective alternative that could help determine whether treatment is helping eradicate the cancer. A startup, Miroculus developed a cheap, open source device that can test blood for several types of cancer at once. The platform, called Miriam finds cancer by extracting RNA from blood and spreading it across plates that look at specific type of mRNA. The technology is then hooked up at a smartphone which sends the information to an online database and compares the microRNA found in the patient’s blood to known patterns indicating different type of cancers in the early stage and can reduce unnecessary cancer screenings.

Nevertheless, experts warn that more studies are essential to regulate the accuracy of the test, exactly which cancers it can detect, at what stages and whether it improves care or survival rates.

SOURCE

https://www.fastcompany.com/3037117/a-new-device-can-detect-multiple-types-of-cancer-with-a-single-blood-test

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356857/

Other related articles published in this Open Access Online Scientific Publishing Journal include the following:

Liquid Biopsy Chip detects an array of metastatic cancer cell markers in blood – R&D @Worcester Polytechnic Institute, Micro and Nanotechnology Lab

Reporters: Tilda Barliya, PhD and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/12/28/liquid-biopsy-chip-detects-an-array-of-metastatic-cancer-cell-markers-in-blood-rd-worcester-polytechnic-institute-micro-and-nanotechnology-lab/

Liquid Biopsy Assay May Predict Drug Resistance

Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2015/11/06/liquid-biopsy-assay-may-predict-drug-resistance/

One blood sample can be tested for a comprehensive array of cancer cell biomarkers: R&D at WPI

Curator: Marzan Khan, B.Sc

https://pharmaceuticalintelligence.com/2017/01/05/one-blood-sample-can-be-tested-for-a-comprehensive-array-of-cancer-cell-biomarkers-rd-wpi

 

 

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Sequence the Human Genome

Curator: Larry H Bernstein, MD, FCAP

 

 

Geneticist Craig Venter helped sequence the human genome. Now he wants yours.

By CARL ZIMMER   NOVEMBER 5, 2015   http://www.statnews.com/2015/11/05/geneticist-craig-venter-helped-sequence-the-human-genome-now-he-wants-yours/

If you enter Health Nucleus, a new facility in San Diego cofounded by J. Craig Venter, one of the world’s best-known living scientists, you will get a telling glimpse into the state of medical science in 2015.

Your entire genome will be sequenced with extraordinary resolution and accuracy. Your body will be scanned in fine, three-dimensional detail. Thousands of compounds in your blood will be measured. Even the microbes that live inside you will be surveyed. You will get a custom-made iPad app to navigate data about yourself. Also, your wallet will be at least $25,000 lighter.

Venter, who came to the world’s attention in the 1990s when he led a campaign to produce the first draft of a human genome, launched Health Nucleus last month as part of his new company, Human Longevity. He has made clear that his aim is just as lofty as it was when he and his team sequenced the human genome or built a flu vaccine from a genetic sequence delivered to them over the Internet.

“We’re trying to show the value of actual scientific data that can change people’s lives,” Venter told STAT in some of his most extensive remarks yet about the project. “Our goal is to interpret everything in the genome that we can.”

Still, the initiative is drawing deep suspicion among some doctors who question whether Venter’s existing tests can tell patients anything meaningful at all. In interviews, they said they see Health Nucleus as the latest venture that could lead consumers to believe that more testing means improved health. That notion, they say, could drive customers to get procedures they don’t need, which might even be harmful.

“I think there is absolutely no evidence that any of those tests have any benefit for healthy people,” Dr. Rita Redberg, a cardiologist at the University of California at San Diego and the editor-in-chief of JAMA Internal Medicine, said when asked about Venter’s new project.

Venter has a black belt in media savvy — he can make the details of molecular biology alluring for viewers of 60 Minutes and TED talks alike — but off screen he has earned a reputation even from his critics for serious scientific achievements. His non-profit J. Craig Venter Institute, which he founded in 1992, now has a staff of 300. Scientists at the institute have explored everything from the ocean’s biodiversity to the Ebola virus.

Last year, at age 67, Venter cofounded Human Longevity, a company based in San Diego with branches in Mountain View, Calif., and Singapore that is building the largest human genome-sequencing operation on Earth, equipped with massive computing resources to analyze the data being generated. The firm’s database now contains highly accurate genome sequences from 20,000 people; another 3,000 genomes are being added each month.

Franz Och, the former head of Google Translate and an expert on machine learning, is leading a team that’s teaching computers to recognize patterns in the company’s databases that scientists themselves may not be able to see. To demonstrate the power of this approach, Human Longevity researchers are using machine learning to discover how genetic variations shape the human face.

“We can determine a good resemblance of your photograph straight from your genetic code,” said Venter.

Venter and his colleagues will be publishing the results of that study soon — most likely generating another round of headlines. But headlines don’t pay the bills, and at a company that’s got $70 million in funding from private investors, bills matter. The company is now exploring a number of avenues for generating income from its database. It has partnered with Discovery, an insurance company in England and South Africa, to read the DNA of their clients. For $250 apiece, it will sequence the protein-coding regions of the genome, known as exomes, and offer an interpretation of the data.

Health Nucleus could become yet another source of income for Human Longevity. The San Diego facility can handle eight to 12 people a day. There are plans to open more sites both in the United States and abroad. “You can do the math,” Venter said.

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Saudi Human Genome Program, International Barcode of Life Project

Reporter: Aviva Lev-Ari, PhD, RN

Life Tech Becomes Partner in Saudi Human Genome Program, International Barcode of Life Project

December 09, 2013

NEW YORK, GenomeWeb − Life Technologies has become a partner in two research projects, the Saudi Human Genome Program and the International Barcode of Life (iBOL) project, the company said this week. The projects will employ the firm’s Ion Proton, capillary electrophoresis, and PGM sequencing technologies.

The goal of the Saudi Human Genome Project, led by Saudi Arabia’s national funding agency, the King Abdulaziz City for Science and Technology (KACST), is to study the genetic basis of disease in Saudi Arabia and the Middle East.

Over the next five years, the project aims to sequence 100,000 genomes from individuals from the region using Life Tech’s Ion Proton technology. Sequencing will be initially conducted at 10 genome centers across Saudi Arabia, with five additional centers to be created in the future.

Life Tech will design and equip the centers, and provide “end-to-end solutions” and services for operations and informatics. Integrated Gulf Biosystems, Life Tech’s distributor in the Middle East, said it played a “pivotal role” in bringing Life Tech’s technology to KACST.

Results from the project will be used to build a Saudi-specific database, providing the basis for future personalized medicine in the Kingdom. Specifically, the information is expected to help with premarital and prenatal screening for rare genetic diseases, as well as for population studies.

SOURCE

http://www.genomeweb.com//node/1321146?utm_source=SilverpopMailing&utm_medium=email&utm_campaign=Management%20Shakeup%20at%20Hologic;%20Life%20Tech%20Partners%20on%20Saudi%20Genome%20Project;%20Cancer%20Driver%20Gene%20Study%20-%2012/09/2013%2010:50:00%20AM

 

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Curator: Aviva Lev-Ari, PhD, RN

In their discussion, the researchers argue that the U.S. Supreme Court now has a chance to shape the balance between the medical good versus inventor protection, adding that, in their opinion, the court should limit the patenting of existing nucleotide sequences, due to their broad scope and non-specificity in the human genome.

“I am extremely pro-patent, but I simply believe that people should not be able to patent a product of nature,” Dr. Mason says. “Moreover, I believe that individuals have an innate right to their own genome, or to allow their doctor to look at that genome, just like the lungs or kidneys. Failure to resolve these ambiguities perpetuates a direct threat to genomic liberty, or the right to one’s own DNA.”

http://www.sciencedaily.com/releases/2013/03/130326101614.htm

Supreme Court May Decide Whether We Own Our Genes

March 26, 2013
 
Image Credit: Photos.com

Brett Smith for redOrbit.com – Your Universe Online

They may be responsible for everything in your life, from conception to death, they may be inside every living cell in your body – but you do not own your own genes, legally speaking.

According to a report in Genome Medicine, patents essentially cover the entire human genome, hampering research and raising the question of “genomic liberty.”

The legal standing of genomic patents could change next month when the Supreme Court reviews patent rights for two key breast and ovarian cancer genes, BRCA1 and BRCA2, which include segments of genetic code as small as 15 nucleotides, known as 15mers.

“This is, so to speak, patently ridiculous,” said report co-author Dr. Christopher E. Mason of Weill Cornell Medical College. “If patent claims that use these small DNA sequences are upheld, it could potentially create a situation where a piece of every gene in the human genome is patented by a phalanx of competing patents.”

In their report, Mason and Dr. Jeffrey Rosenfeld, an assistant professor of medicine at the University of Medicine & Dentistry of New Jersey, looked at patents for two different categories of DNA fragments:

  • long and
  • short.

They revealed 41 percent of the human genome is covered by “long” DNA patents that can include whole genes. Because many genes share similar sequences within their code that are patented, the combination of all these “short” DNA patents covers 100 percent of the genome.

“This demonstrates that short patent sequences are extremely non-specific and that a 15mer claim from one gene will always cross-match and patent a portion of another gene as well,” Mason said. “This means it is actually impossible to have a 15mer patent for just one gene.”

To reach their conclusions, the researchers first looked at small sequences within BRCA1 and noticed one of the company’s BRCA1 patents also covered almost 690 other human genes. Some of these genes are unrelated to breast cancer – instead being associated with brain development and heart functioning.

Next, researchers determined how many known genes are covered by 15mers in current patent claims. They found 58 patents covered at least ten percent of all bases of all human genes. The broadest patent claim matched 91.5 percent of human genes. When the team took patented 15mers and matched them to known genes, they found 100 percent of known genes are patented.

Finally, the team also looked at “long” DNA sequences from existing gene patents, ranging from a few dozen to thousands of base pairs. They found these long sequences added up to 41 percent of known human genes.

“There is a real controversy regarding gene ownership due to the overlap of many competing patent claims. It is unclear who really owns the rights to any gene,” Rosenfeld said. “While the Supreme Court is hearing one case concerning just the BRCA1 patent, there are also many other patents whose claims would cover those same genes.

“Do we need to go through every gene to look at who made the first claim to that gene, even if only one small part? If we resort to this rule, then the first patents to be granted for any DNA will have a vast claim over portions of the human genome,” he added.

Another legal question surrounds patented DNA sequences that cross species boundaries. The researchers found one company has the rights to 84 percent of all human genes for a patent they received for cow breeding.

Source: Brett Smith for redOrbit.com – Your Universe Online

Topics: Health Medical PharmaGeneticsGene patentBiologyGeneLiving modified organismAssociation for Molecular Pathology v. U.S. Patent and Trademark OfficeBRCA1DNASupreme CourtHuman genome

SOURCE:

Human Genome: Name Your Price

Posted March 27, 2013 – 12:51 by a staff writer

Weill Cornell Medical College researchers have issued a warning that, according to the patent system, the vast majority of humans on the planet don’t ‘own’ their own genes, and in fact their biological make-up is being exploited for profit. Even seemingly innocent research into cow breeding can cover human genetic make-up.

As spotted by a Slashdot user, two researchers combing through patents on human DNA discovered that over 40,000 patents on DNA molecules have effectively declared the human genome for profit. A report in medical journal Genome Medicine said that humans may be losing their grip on “individual genomic liberty”.

Looking at two kinds of patented DNA sequences, or long and short fragments, 41 percent of the human genome is covered by DNA patents that can cover entire genes. According to the research, if all of the short sequence patents were allowed in aggregate they could cover 100 percent of the human genome.

Lead author Dr Christopher E Mason and co-author Dr Jeffrey Rosenfeld warned that short sequences from patents cover “virtually the entire genome, even outside of genes”. A Weill Cornell assistant professor asked: “How is it possible that my doctor cannot look at my DNA without being concerned about patent infringement?”

There will be a Supreme Court hearing about genomic patent rights next month that will debate the morality of a molecular diagnostic company claiming patents on key cancer genes, as well as on any small sequence of code within the BRCA1 gene. Cornell explained that at present, genes are able to be patented by researchers working in companies and institutions who discover genes that have potentially useful applications, like in testing for cancer risks. Because the patents can be held by companies or organisations, it is possible for the patent owner to charge doctors thousands of dollars for each diagnostic test.

The authors pointed out that in their studies, while engaged in research, it is common to come across a gene that’s patented “almost every day”. Their paper promises to examine how genes may have been impacted by held patents, and the extent of intellectual property on the genome. Gene patents can also relate between different species – for example, a company may have a patent for breeding cows that also covers a large percentage of human genes. They cited one company that owns 84 percent of all human genes because of a patent for cow breeding.

“There is a real controversy regarding gene ownership due to the overlap of many competing patent claims. It is unclear who really owns the rights to any gene,” Dr Rosenfeld said. “Do we need to go through every gene to look at who made the first claim to that gene, even if only one small part? If we resort to this rule, then the first patents to be granted for any DNA will have a vast claim over portions of the human genome.”

Lead author Dr Mason insisted he is pro-patent, but believes people “should not be able to patent a product of nature”.

“I believe that individals have an innate right to their own genome,” he said.

http://www.tgdaily.com/hardware-brief/70513-human-genome-name-your-price#BUKfEtjWKb3gq7X3.99 

Other related articles on Genomics and Ethics on this Open Access Online Scientific Journal include the following:

Aviva Lev-Ari, PhD, RN

20.2 Understanding the Role of Personalized Medicine

Larry H Bernstein, MD, FACP

20.3 Attitudes of Patients about Personalized Medicine

Larry H Bernstein, MD, FACP

20.4  Genome Sequencing of the Healthy

Larry H. Bernstein, MD, FACP and Aviva Lev-Ari, PhD, RN

20.5   Genomics in Medicine – Tomorrow’s Promise

Larry H. Bernstein, MD, FACP

20.6  The Promise of Personalized Medicine

Larry H. Bernstein, MD, FACP

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Curators: Aviva Lev-Ari, PhD, RN and Larry Bernstein, MD, FACP

The essence of the message is summarized by Larry Bernstein, MD, FACP, as follows:

[1] we employ a massively parallel reporter assay (MPRA) to measure the transcriptional levels induced by 145bp DNA segments centered on evolutionarily-conserved regulatory motif instances and found in enhancer chromatin states
[2] We find statistically robust evidence that (1) scrambling, removing, or disrupting the predicted activator motifs abolishes enhancer function, while silent or motif-improving changes maintain enhancer activity; (2) evolutionary conservation, nucleosome exclusion, binding of other factors, and strength of the motif match are all associated with wild-type enhancer activity; (3) scrambling repressor motifs leads to aberrant reporter expression in cell lines where the enhancers are usually not active.
[3] Our results suggest a general strategy for deciphering cis-regulatory elements by systematic large-scale experimental manipulation, and provide quantitative enhancer activity measurements across thousands of constructs that can be mined to generate and test predictive models of gene expression.

Manolis Kellis and co-authors from the Massachusetts Institute of Technology and the Broad Institute describe a massively parallel reporter assay that they used to systematically study regulatory motifs falling within thousands of predicted enhancer sequences in the human genome. Using this assay, they examined 2,104 potential enhancers in two human cell lines, along with another 3,314 engineered enhancer variants. “Our results suggest a general strategy for deciphering cis-regulatory elements by systematic large-scale experimental manipulation,” they write, “and provide quantitative enhancer activity measurements across thousands of constructs that can be mined to generate and test predictive models of gene expression.”

SOURCE:

http://www.genomeweb.com//node/1206571?hq_e=el&hq_m=1536519&hq_l=4&hq_v=e1df6f3681

Systematic dissection of regulatory motifs in 2,000 predicted human enhancers using a massively parallel reporter assay

  1. Pouya Kheradpour1,
  2. Jason Ernst1,
  3. Alexandre Melnikov2,
  4. Peter Rogov2,
  5. Li Wang2,
  6. Xiaolan Zhang2,
  7. Jessica Alston2,
  8. Tarjei S Mikkelsen2 and
  9. Manolis Kellis1,3

+Author Affiliations


  1. 1 MIT;

  2. 2 Broad Institute
  1. * Corresponding author; email: manoli@mit.edu

Abstract

Genome-wide chromatin maps have permitted the systematic mapping of putative regulatory elements across multiple human cell types, revealing tens of thousands of candidate distal enhancer regions. However, until recently, their experimental dissection by directed regulatory motif disruption has remained unfeasible at the genome scale, due to the technological lag in large-scale DNA synthesis. Here, we employ a massively parallel reporter assay (MPRA) to measure the transcriptional levels induced by 145bp DNA segments centered on evolutionarily-conserved regulatory motif instances and found in enhancer chromatin states. We select five predicted activators (HNF1, HNF4, FOXA, GATA, NFE2L2) and two predicted repressors (GFI1, ZFP161) and measure reporter expression in erythroleukemia (K562) and liver carcinoma (HepG2) cell lines. We test 2,104 wild-type sequences and an additional 3,314 engineered enhancer variants containing targeted motif disruptions, each using 10 barcode tags in two cell lines and 2 replicates. The resulting data strongly confirm the enhancer activity and cell type specificity of enhancer chromatin states, the ability of 145bp segments to recapitulate both, the necessary role of regulatory motifs in enhancer function, and the complementary roles of activator and repressor motifs. We find statistically robust evidence that (1) scrambling, removing, or disrupting the predicted activator motifs abolishes enhancer function, while silent or motif-improving changes maintain enhancer activity; (2) evolutionary conservation, nucleosome exclusion, binding of other factors, and strength of the motif match are all associated with wild-type enhancer activity; (3) scrambling repressor motifs leads to aberrant reporter expression in cell lines where the enhancers are usually not active. Our results suggest a general strategy for deciphering cis-regulatory elements by systematic large-scale experimental manipulation, and provide quantitative enhancer activity measurements across thousands of constructs that can be mined to generate and test predictive models of gene expression.

  • Received June 26, 2012.
  • Accepted March 14, 2013.

This manuscript is Open Access.

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.

SOURCE:

http://genome.cshlp.org/content/early/2013/03/19/gr.144899.112.abstract

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Gene Sequencing – to the Bedside

Reporter: Larry H Bernstein, MD, FCAP

Gene sequencing leaves the laboratory

Maturing technology speeds medical diagnoses.
Erika Check Hayden  19 February 2013
The steep fall in the cost of sequencing a genome has, for the moment, slowed. Yet researchers attending this year’s Advances in Genome Biology and Technology (AGBT) meeting in Marco Island, Florida, on 20–23 February are not complaining. At a cost as low as US$5,000–10,000 per human genome, sequencing has become cheap and reliable enough that researchers are not waiting for the next sequencing machine to perfect new applications in medicine.
Single-cell genomics is allowing fertility clinics to screen embryos for abnormalities more cheaply.
Human genome to genes

Human genome to genes (Photo credit: Wikipedia)

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