Tag: rna

Bioethics News

American CRISPR Experiments and the Future of Regulation

By Michael S. Dauber, MA, GBI Visiting Scholar

According to a report in The MIT Technology Review, researchers in a lab based in Portland, Oregon have successfully created genetically modified human embryos for the first time in U.S. history, using a technique called CRISPR. The project, directed by Shoukhrat Mitalipov, a researcher at Oregon Health and Science University, was published in Nature, and consisted of modifying the genes of human embryos to prevent a severe, genetically inherited heart condition. The embryos were destroyed several days after the experiments.

CRISPR stands for “clustered, regularly interspaced, short palindromic repeats.” It is a genetic editing technique that allows scientists to cut out pieces of DNA and replace them with other pieces. CRISPR originated as a naturally occurring cellular defense system in certain bacterial that allows a cell to defend itself from foreign genetic material injected into cells by viruses. RNA strands that match the problematic genes bind with the piece of DNA to be removed, and enzymes work to remove the defective material. When CRISPR is used to edit the human genome, scientists apply CRISPR RNA strands and the corresponding enzymes that match the genes they wish to edit in order to extract the problematic genes.

Mitalipov is not the first scientist to use CRISPR to edit the human genome. Scientists in China have been using the technique in research using human embryos dating back to 2015. One notable study consisted of attempts to make cells resistant to HIV. Another controversial study involved the injection of CRISPR-modified cells into a patient with advanced lung cancer.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics News

CRISPR diagnoisis tool. A new biomedical breakthrough from genome editing to disease diagnosis

CRISPR techniques are gaining traction in another realm of medical technology. CRISPR diagnosis tool

It has recently been announced that the CRISPR tool, used up to now in the field of genome editing, can be used in another field, namely in diagnosis, combining it with the enzyme Cas13a instead of with Cas9 (See HERE). By combining CRISPR with the new enzyme, discovered by researchers at the University of California, Berkeley, investigators can quickly and cheaply detect several specific RNA sequences at the same time, including the RNA of some viruses, such as Zika. This new use does not fall within the field of genome editing, so it does not share its bioethical issues, but it is a major biomedical breakthrough.

La entrada CRISPR diagnoisis tool. A new biomedical breakthrough from genome editing to disease diagnosis aparece primero en Bioethics Observatory.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Huntington’s Disease: Gene Editing Shows Promise in Mouse Studies

My father was a folk song collector, and I grew up listening to the music of Woody Guthrie. On July 14th, folk music enthusiasts will be celebrating the 105th anniversary of Guthrie’s birth in his hometown of Okemah, OK. Besides being renowned for writing “This Land is Your Land” and other folk classics, Guthrie has another more tragic claim to fame: he provided the world with a glimpse at the devastation caused by a rare, inherited neurological disorder called Huntington’s disease.

When Guthrie died from complications of Huntington’s a half-century ago, the disease was untreatable. Sadly, it still is. But years of basic science advances, combined with the promise of innovative gene editing systems such as CRISPR/Cas9, are providing renewed hope that we will someday be able to treat or even cure Huntington’s disease, along with many other inherited disorders.

My own lab was part of a collaboration of seven groups that identified the Huntington’s disease gene back in 1993. Huntington’s disease occurs when a person inherits from one parent a mutant copy of the huntingtin (HTT) gene that contains extra repetitions, or a “stutter,” of three letters (CAG) in DNA’s four-letter code. This stutter leads to production of a misfolded protein that is toxic to the brain’s neurons, triggering a degenerative process that, over time, leads to mood swings, slurred speech, uncontrolled movements, and, eventually, death. In a new study involving a mouse model of Huntington’s disease, researchers were able to stop the production of the abnormal protein by using CRISPR tools to cut the stutter out of the mutant gene.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Creative Minds: Rapid Testing for Antibiotic Resistance

Ahmad (Mo) Khalil

The term “freeze-dried” may bring to mind those handy MREs (Meals Ready to Eat) consumed by legions of soldiers, astronauts, and outdoor adventurers. But if one young innovator has his way, a test that features freeze-dried biosensors may soon be a key ally in our nation’s ongoing campaign against the very serious threat of antibiotic-resistant bacterial infections.

Each year, antibiotic-resistant infections account for more than 23,000 deaths in the United States. To help tackle this challenge, Ahmad (Mo) Khalil, a researcher at Boston University, recently received an NIH Director’s New Innovator Award to develop a system that can more quickly determine whether a patient’s bacterial infection will respond best to antibiotic X or antibiotic Y—or, if the infection is actually viral rather than bacterial, no antibiotics are needed at all.

To build the foundation for his new diagnostic approach, Khalil is sequencing the transcriptomes of a variety of bacterial strains to analyze their genomic response to various antibiotics. He then uses that information to produce a panel of RNA sensors specific to each particular bacterial strain, and freeze-dries those sensors onto strips of testing paper, creating what he thinks will be a highly specific diagnostic test with a very long shelf life.

As Khalil envisions it, the clinical use of his test would involve obtaining a sample of infected material from a patient and exposing the sample to a certain antibiotic. After about 20 minutes, the sample’s cells would be lysed and the resulting solution placed on the test strip. That liquid would serve to reconstitute the freeze-dried RNA sensor reactions embedded on the paper, and those sensors would light up if the sample contains a bacterium that is a good candidate for the antibiotic.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics News

An Epigenetics Gold Rush: New Controls for Gene Expression

February 22, 2017

(Nature) – Nine years later, such research has given birth to an ‘ome of its own, the epitranscriptome. He and others have shown that a methyl group attached to adenine, one of the four bases in RNA, has crucial roles in cell differentiation, and may contribute to cancer, obesity and more. In 2015, He’s lab and two other teams uncovered the same chemical mark on adenine bases in DNA (methyl marks had previously been found only on cytosine), suggesting that the epigenome may be even richer than previously imagined. Research has taken off.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Find and Replace: DNA Editing Tool Shows Gene Therapy Promise

Caption: This image represents an infection-fighting cell called a neutrophil. In this artist’s rendering,  the cell’s DNA is being “edited” to help restore its ability to fight bacterial invaders.
Credit: NIAID, NIH

For gene therapy research, the perennial challenge has been devising a reliable way to insert safely a working copy of a gene into relevant cells that can take over for a faulty one. But with the recent discovery of powerful gene editing tools, the landscape of opportunity is starting to change. Instead of threading the needle through the cell membrane with a bulky gene, researchers are starting to design ways to apply these tools in the nucleus—to edit out the disease-causing error in a gene and allow it to work correctly.

While the research is just getting under way, progress is already being made for a rare inherited immunodeficiency called chronic granulomatous disease (CGD). As published recently in Science Translational Medicine, a team of NIH researchers has shown with the help of the latest CRISPR/Cas9 gene-editing tools, they can correct a mutation in human blood-forming adult stem cells that triggers a common form of CGD. What’s more, they can do it without introducing any new and potentially disease-causing errors to the surrounding DNA sequence [1].

When those edited human cells were transplanted into mice, the cells correctly took up residence in the bone marrow and began producing fully functional white blood cells. The corrected cells persisted in the animal’s bone marrow and bloodstream for up to five months, providing proof of principle that this lifelong genetic condition and others like it could one day be cured without the risks and limitations of our current treatments.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics News

CRISPR Screening Identifies Potential HIV Treatment Targets

December 20, 2016

(Eurekalert) – Investigators from the Ragon Institute of MGH, MIT and Harvard and the Broad Institute of MIT and Harvard have used the revolutionary new gene-editing technology CRISPR-Cas9 to identify three promising new targets for treatment of HIV infection. In their report receiving advance online publication in Nature Genetics, the research team describes how screening with CRISPR for human genes essential for HIV infection but not for cellular survival identified five genes — three of which had not been identified in earlier studies using RNA interference. Their method can also be used to identify therapeutic targets for other viral pathogens.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Creative Minds: Modeling Neurobiological Disorders in Stem Cells

Feng Zhang

Most neurological and psychiatric disorders are profoundly complex, involving a variety of environmental and genetic factors. Researchers around the world have worked with patients and their families to identify hundreds of possible genetic leads to learn what goes wrong in autism spectrum disorder, schizophrenia, and other conditions. The great challenge now is to begin examining this growing cache of information more systematically to understand the mechanism by which these gene variants contribute to disease risk—potentially providing important information that will someday lead to methods for diagnosis and treatment.

Meeting this profoundly difficult challenge will require a special set of laboratory tools. That’s where Feng Zhang comes into the picture. Zhang, a bioengineer at the Broad Institute of MIT and Harvard, Cambridge, MA, has made significant contributions to a number of groundbreaking research technologies over the past decade, including optogenetics (using light to control brain cells), and CRISPR/Cas9, which researchers now routinely use to edit genomes in the lab [1,2].

Zhang has received a 2015 NIH Director’s Transformative Research Award to develop new tools to study multiple gene variants that might be involved in a neurological or psychiatric disorder. Zhang draws his inspiration from nature, and the microscopic molecules that various organisms have developed through the millennia to survive. CRISPR/Cas9, for instance, is a naturally occurring bacterial defense system that Zhang and others have adapted into a gene-editing tool.

With the Transformative Research Award, Zhang will turn his toolmaking efforts toward human stem cells. Many of the variants he will introduce into these cells are outside the protein-coding regions of genes, because that’s where many of the DNA variations in neurological or psychiatric disorders have been found.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Sickle Cell Disease: Gene-Editing Tools Point to Possible Ultimate Cure

Caption: An electron micrograph showing two red blood cells, one normal (right) and the other (left) deformed by crystalline hemoglobin into the “sickle” shape characteristic of patients with sickle cell disease.
Credit: Frans Kuypers: RBClab.com, UCSF Benioff Children’s Hospital Oakland

Scientists first described the sickle-shaped red blood cells that give sickle cell disease its name more than a century ago. By the 1950s, the precise molecular and genetic underpinnings of this painful and debilitating condition had become clear, making sickle cell the first “molecular disease” ever characterized. The cause is a single letter “typo” in the gene encoding oxygen-carrying hemoglobin. Red blood cells containing the defective hemoglobin become stiff, deformed, and prone to clumping. Individuals carrying one copy of the sickle mutation have sickle trait, and are generally fine. Those with two copies have sickle cell disease and face major medical challenges. Yet, despite all this progress in scientific understanding, nearly 70 years later, we still have no safe and reliable means for a cure.

Recent advances in CRISPR/Cas9 gene-editing tools, which the blog has highlighted in the past, have renewed hope that it might be possible to cure sickle cell disease by correcting DNA typos in just the right set of cells. Now, in a study published in Science Translational Medicine, an NIH-funded research team has taken an encouraging step toward this goal [1]. For the first time, the scientists showed that it’s possible to correct the hemoglobin mutation in blood-forming human stem cells, taken directly from donors, at a frequency that might be sufficient to help patients.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Creative Minds: Building the RNA Toolbox

Caption: Genetically identical mice. The Agouti gene is active in the yellow mouse and inactive in the brown mouse.
Credit: Dana Dolinoy, University of Michigan, Ann Arbor, and Randy Jirtle, Duke University, Durham, NC

Step inside the lab of Dana Dolinoy at the University of Michigan, Ann Arbor, and you’re sure to hear conversations that include the rather strange word “agouti” (uh-goo-tee). In this context, it’s a name given to a strain of laboratory mice that arose decades ago from a random mutation in the Agouti gene, which is normally expressed only transiently in hair follicles. The mutation causes the gene to be turned on, or expressed, continuously in all cell types, producing mice that are yellow, obese, and unusually prone to developing diabetes and cancer. As it turns out, these mutant mice and the gene they have pointed to are more valuable than ever today because they offer Dolinoy and other researchers an excellent model for studying the rapidly emerging field of epigenomics.

The genome of the mouse, just as for the human, is the complete DNA instruction book; it contains the coding information for building the proteins that carry out a variety of functions in a cell. But modifications to the DNA determine its function, and these are collectively referred to as the epigenome. The epigenome is made up of chemical tags and proteins that can attach to the DNA and direct such actions as turning genes on or off, thereby controlling the production of proteins in particular cells. These tags have different patterns in each cell type, helping to explain, for example, why a kidney and a skin cell can behave so differently when they share the same DNA.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.