CRISPR & Genetic Engineering News and Discussions

[Yuli Ban]

Move over CRISPR, the retrons are coming

While the CRISPR-Cas9 gene editing system has become the poster child for innovation in synthetic biology, it has some major limitations. CRISPR-Cas9 can be programmed to find and cut specific pieces of DNA, but editing the DNA to create desired mutations requires tricking the cell into using a new piece of DNA to repair the break. This bait-and-switch can be complicated to orchestrate, and can even be toxic to cells because Cas9 often cuts unintended, off-target sites as well.

Alternative gene editing techniques called recombineering instead perform this bait-and-switch by introducing an alternate piece of DNA while a cell is replicating its genome, efficiently creating genetic mutations without breaking DNA. These methods are simple enough that they can be used in many cells at once to create complex pools of mutations for researchers to study. Figuring out what the effects of those mutations are, however, requires that each mutant be isolated, sequenced, and characterized: a time-consuming and impractical task.

Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard Medical School (HMS) have created a new gene editing tool called Retron Library Recombineering (RLR) that makes this task easier. RLR generates up to millions of mutations simultaneously, and "barcodes" mutant cells so that the entire pool can be screened at once, enabling massive amounts of data to be easily generated and analyzed. The achievement, which has been accomplished in bacterial cells, is described in a recent paper in PNAS.

[weatheriscool]

Man blind for 40 years regains some sight through gene therapy

Doctors for the first time have used a form of gene therapy to restore partial vision in a blind person, according to findings announced Monday.

The research team genetically altered retinal ganglion cells to become light-sensitive in a man whose vision was destroyed by retinitis pigmentosa, a genetic disorder that breaks down cells that absorb and convert light into brain signals.

Using special goggles, the 58-year-old man went from total blindness to being able to detect a large notebook, a smaller staple box, glass tumblers and even the stripes of a street crosswalk, researchers reported in the June issue of the journal Nature Medicine.

https://medicalxpress.com/news/2021-05- ... erapy.html

[wjfox]

U.K. set to loosen rules for gene-edited crops and animals

May. 26, 2021, 2:30 PM

When Boris Johnson became prime minister of the United Kingdom in 2019, he pledged to “liberate the U.K.’s extraordinary bioscience sector from anti–genetic modification rules.” The country had to hew to strict European biotech regulations until it finalized its divorce from the European Union in January. Next month, the government is widely expected to follow through on Johnson’s promise by making it easier to test and commercialize some genetically engineered crops and livestock.

The decision, which will be announced by 17 June, applies to plants and animals whose genes have been edited with precision techniques such as CRISPR. It will put the United Kingdom in line with several countries including the United States, and U.K. biotechnologists say it will speed research and stimulate investment.

“Much as I have to swallow hard and say it through gritted teeth, Brexit has at least one dividend,” says Jonathan Jones, a plant biologist at the Sainsbury Laboratory, a nonprofit center investigating plant disease resistance. Tina Barsby, CEO of the National Institute of Agricultural Botany, says the shift may be “the most significant policy breakthrough in plant breeding for more than 2 decades.”

Read more: https://www.sciencemag.org/news/2021/05 ... nd-animals



Credit: JOHN INNES CENTRE/FLICKR

[wjfox]

'Gene therapy is a game changer for our son'

8 hours ago

Baby Arthur is just five months old. He has no way of knowing the treatment he is receiving in his right arm is the world's most costly medicine.

His devastating progressive disorder causes loss of muscle control.

But he has become one of the first patients to be treated on the NHS with Zolgensma, a gene therapy with a list price of £1.795m.

[...]

The drug contains a healthy copy of a missing or faulty gene called SMN1.

This is inserted into a harmless virus.

In the body, the virus delivers the replacement gene into the nucleus of motor neuron cells.

https://www.bbc.co.uk/news/uk-57309613

[weatheriscool]

Tweaking gene therapy: Scientists experimentally boost red blood cells to aid sickle cell and other hemoglobin diseases
https://medicalxpress.com/news/2021-05- ... tally.html
by Delthia Ricks , Medical Xpress

A series of laboratory studies is underway in the United States to improve gene therapy worldwide for sickle cell disease, a complex and sometimes deadly heritable blood disorder that dramatically affects the structure and function of oxygen-ferrying red blood cells.

Sickle cell disease is a devastating disorder that largely affects people of African descent. The genetic condition derives its name from the shape of patients' red blood cells, which have the configuration of a crescent moon or sickle. As one of the heritable hemoglobin diseases, doctors say the condition is related to beta thalassemia, which is largely seen in populations throughout the Mediterranean, parts of the Mideast and Asia. In that disease, red blood cells do not sickle but are substantially smaller than normal, and likewise are impaired as transporters of oxygen.

[weatheriscool]

Gene therapy more cost effective than current treatments for hemophilia B
https://medicalxpress.com/news/2021-06- ... ments.html
by St. Jude Children's Research Hospital

A St. Jude Children's Research Hospital analysis found a major gap between the cost to manufacture and distribute hemophilia B gene therapy and the $2 million-plus price reportedly under consideration for hemophilia gene therapy now in development.

The study appeared online in the journal Blood. It is the first to report gene therapy production costs.

St. Jude researchers have pioneered and produced gene therapy for several disorders, including hemophilia B. This inherited bleeding disorder affects about 1 in 30,000 people, primarily men.

The analysis relied on the hospital's own cost data. Researchers calculated the total per-patient cost of manufacture, distribution and five-year follow-up of gene therapy for severe hemophilia B patients as $87,198.

[Yuli Ban]

One CRISPR Treatment Lowered Cholesterol in Monkeys by 60 Percent

More than one in three American adults have high cholesterol, which can lead to serious health problems like heart disease and stroke. The best remedies we have right now are cholesterol-lowering drugs called statins, a diet rich in vegetables and low in fat, and good old-fashioned exercise. But in the future, there may be another way to reduce our cholesterol levels.

A study published last week in Nature described how a team of scientists from the University of Pennsylvania and biotech company Verve Therapeutics used the gene editing tool CRISPR to lower LDL cholesterol in monkeys by 60 percent in just one week. And, the monkeys’ cholesterol levels stayed low for over eight months after a single dose of the treatment.

[weatheriscool]

Researchers improve efficiency and accessibility of CRISPR
https://phys.org/news/2021-06-efficienc ... rispr.html
by California Institute of Technology

One of the most powerful tools available to biologists these days is CRISPR-Cas9, a combination of specialized RNA and protein that acts like a molecular scalpel, allowing researchers to precisely slice and dice pieces of an organism's genetic code.

But even though CRISPR-Cas9 technology has offered an unprecedented level of control for those studying genetics and genetic engineering, there has been room for improvement. Now, a new technique developed at Caltech by biology graduate student Shashank "Sha" Gandhi in the lab of Marianne Bronner, Distinguished Professor of Biology and director of the Beckman Institute, is taking CRISPR-Cas9 accessibility to the next level.

In a paper appearing in the journal Development, Gandhi and members of Bronner's lab describe the new technique, which has been designed specifically to disable or remove genes from a genome. This is known as "knocking out" a gene.

[Yuli Ban]

[weatheriscool]

A remote control for gene transfer
https://phys.org/news/2021-06-remote-gene.html
by University of Freiburg

The ability to insert desirable genes into animal or human cells is the basis of modern life science research and of widespread biomedical applications. The methods used to date for this purpose are mostly non-specific, making it difficult for scientists to control which cell will or will not take up a gene.

For this gene transfer, the target genes are often packaged into 'viral vectors.' These are viruses in which part of the genetic material has been replaced by the target genes. When researchers add these viral vectors to cells, the vectors introduce the genes into the cells. This is the principle behind some of the current SARS-CoV-2 vaccines such as those from AstraZeneca or Johnson&Johnson. However, it is difficult—even impossible—to control into which cells the target genes enter, since the viral vectors tend to dock non-specifically onto all cells of a certain cell type. A team of researchers from the Cluster of Excellence CIBSS—Centre for Integrative Biological Signalling Studies at the University of Freiburg, led by Dr. Maximilian Hörner, Prof. Dr. Wolfgang Schamel and Prof. Dr. Wilfried Weber, has developed a new technology that enables them to introduce target genes in a controlled manner and thereby control processes in individual selected cells. The researchers have published their work in the current issue of Science Advances.

[weatheriscool]

Genetic engineering is probably what allows for life extension, the end of cancer, heart disease and hell maybe a vastly superior human species if we're smart. It is very promising.

[weatheriscool]

New drugs may kill and limit reproduction of bowel cancer cells

by Hudson Institute of Medical Research
https://medicalxpress.com/news/2021-06- ... ancer.html

Drugs that are being trialed to treat leukemia could also be used to fight bowel cancer after a breakthrough by Hudson Institute of Medical Research scientists.

In a world-first, researchers found that the drugs could potentially be used to fight bowel cancer, using Nobel Prize-winning genetic screening technology CRISPR.

The researchers were using CRISPR to identify new targets for bowel cancer tumors when they realized that the gene KMT2A—usually associated with Acute Myeloid Leukemia—promotes bowel cancer. It does this by fuelling uncontrolled growth of the tumor, and encouraging the cancer cells ability to 'self-renew," preventing the tumor from regression or differentiation.

They then trialed two agents that inhibit KMT2A and found that these block bowel cancer growth and self-renewal, with very little damage to normal cells. These inhibitors are very similar to others which are currently in clinical trials to treat leukemia.

[weatheriscool]

mRNA vaccine yields full protection against malaria in mice
https://medicalxpress.com/news/2021-06- ... laria.html
by Walter Reed Army Institute of Research

Scientists from the Walter Reed Army Institute of Research and Naval Medical Research Center partnered with researchers at the University of Pennsylvania and Acuitas Therapeutics to develop a novel vaccine based on mRNA technology that protects against malaria in animal models, publishing their findings in npj Vaccines.

In 2019, there were an estimated 229 million cases of malaria and 409,000 deaths globally, creating an extraordinary cost in terms of human morbidity, mortality, economic burden, and regional social stability. Worldwide, Plasmodium falciparum is the parasite species which causes the vast majority of deaths. Those at highest risk of severe disease include pregnant women, children and malaria naïve travelers. Malaria countermeasures development has historically been a priority research area for the Department of Defense as the disease remains a top threat to U.S. military forces deployed to endemic regions.

[Yuli Ban]

UMD introduces new CRISPR 3.0 system for highly efficient gene activation in plants

In a study in Nature Plants, Yiping Qi, associate professor of Plant Science at the University of Maryland (UMD), introduces a new and improved CRISPR 3.0 system in plants, focusing on gene activation instead of traditional gene editing. This third generation CRISPR system focuses on multiplexed gene activation, meaning that it can boost the function of multiple genes simultaneously. According to the researchers, this system boasts four to six times the activation capacity of current state-of-the-art CRISPR technology, demonstrating high accuracy and efficiency in up to seven genes at once. While CRISPR is more often known for its gene editing capabilities that can knock out genes that are undesirable, activating genes to gain functionality is essential to creating better plants and crops for the future.
"While my lab has produced systems for simultaneous gene editing [multiplexed editing] before, editing is mostly about generating loss of function to improve the crop," explains Qi. "But if you think about it, that strategy is finite, because there aren't endless genes that you can turn off and actually still gain something valuable. Logically, it is a very limited way to engineer and breed better traits, whereas the plant may have already evolved to have different pathways, defense mechanisms, and traits that just need a boost. Through activation, you can really uplift pathways or enhance existing capacity, even achieve a novel function. Instead of shutting things down, you can take advantage of the functionality already there in the genome and enhance what you know is useful."

[Yuli Ban]

He Inherited A Devastating Disease. A CRISPR Gene-Editing Breakthrough Stopped It

Patrick Doherty had always been very active. He trekked the Himalayas and hiked trails in Spain.

But about a year and a half ago, he noticed pins and needles in his fingers and toes. His feet got cold. And then he started getting out of breath any time he walked his dog up the hills of County Donegal in Ireland where he lives.

"I noticed on some of the larger hill climbs I was getting a bit breathless," says Doherty, 65. "So I realized something was wrong."

Doherty found out he had a rare, but devastating inherited disease — known as transthyretin amyloidosis — that had killed his father. A misshapen protein was building up in his body, destroying important tissues, such as nerves in his hands and feet and his heart.

Doherty had watched others get crippled and die difficult deaths from amyloidosis.

"It's terrible prognosis," Doherty says. "This is a condition that deteriorates very rapidly. It's just dreadful."

So Doherty was thrilled when he found out that doctors were testing a new way to try to treat amyloidosis. The approach used a revolutionary gene-editing technique called CRISPR, which allows scientists to make very precise changes in DNA.

"I thought: Fantastic. I jumped at the opportunity," Doherty says.

[weatheriscool]

CRISPR used to treat rare genetic disease in promising phase 1 trial
By Michael Irving
June 27, 2021
https://newatlas.com/medical/crispr-pha ... osis-attr/

Scientists are reporting the first clinical data showing that CRISPR gene editing can be done safely and effectively inside the body. CRISPR was injected directly into the bloodstream of patients with a rare genetic disease, and appeared to work better than current treatments with no serious side effects.

The CRISPR gene-editing tool, which makes precise cut-and-paste edits to the genome inside cells, has shown tremendous promise in treating a wide range of diseases. It’s currently the subject of many human trials, but in almost all of them the actual editing takes place outside the body – cells are removed from the patient, edited and then returned to the body. Another recent study involved injections of CRISPR into the eye to correct a genetic form of blindness, but the results have yet to be published.

Now researchers have released interim data of the first six patients in an ongoing Phase 1 trial conducted by Intellia Therapeutics and Regeneron Pharmaceuticals, marking the first published results of a CRISPR clinical trial involving human gene editing in vivo.

The trial is investigating a CRISPR candidate called NTLA-2001 as a treatment for a disease called transthyretin amyloidosis (ATTR amyloidosis). This rare hereditary disease occurs due to mutations in the TTR gene, which causes a patient to produce misfolded transthyretin (TTR) proteins. These abnormal proteins then build up on nerves and around organs, leading to pain and complications, and can be fatal.

[weatheriscool]

Sweet success: First precision breeding of sugarcane with CRISPR-Cas9
https://phys.org/news/2021-07-sweet-suc ... -cas9.html
by University of Illinois at Urbana-Champaign

Sugarcane is one of the most productive plants on Earth, providing 80 percent of the sugar and 30 percent of the bioethanol produced worldwide. Its size and efficient use of water and light give it tremendous potential for the production of renewable value-added bioproducts and biofuels.

But the highly complex sugarcane genome poses challenges for conventional breeding, requiring more than a decade of trials for the development of an improved cultivar.

Two recently published innovations by University of Florida researchers at the Department of Energy's Center for Advanced Bioenergy and Bioproducts Innovation (CABBI) demonstrated the first successful precision breeding of sugarcane by using CRISPR/Cas9 genome editing—a far more targeted and efficient way to develop new varieties.

[weatheriscool]

Gene therapy success offers hope for reversing rare genetic diseases
By Rich Haridy
July 12, 2021
https://newatlas.com/medical/gene-thera ... -children/

A landmark study published in the journal Nature Communications is describing the extraordinarily successful results of a Phase 1 trial testing a targeted gene therapy for children with a rare genetic disease. The research demonstrates a novel method for delivering gene therapies to specific locations deep in the brain and suggests these kinds of genetic treatments could reverse damage in older subjects born with developmental diseases.

The research focused on children born with a very rare genetic disorder called AADC deficiency. The condition involves a single gene mutation that leads to a deficiency in synthesizing key neurotransmitters – dopamine and serotonin. Children born with the disease suffer severe developmental deficits and motor disabilities, often leaving them unable to speak or feed themselves.

[weatheriscool]

Gene editing 'blocks virus transmission' in human cells

Researchers in Australia said the tool was effective against viral transmissions in lab tests, adding that they hope soon to begin animal trials on the method.

Scientists have used CRISPR gene-editing technology to successfully block the transmission of the SARS-CoV-2 virus in infected human cells, according to research released Tuesday that could pave the way for COVID-19 treatments.

Writing in the journal Nature Communications, researchers in Australia said the tool was effective against viral transmissions in lab tests, adding that they hoped to begin animal trials soon.

CRISPR, which allows scientists to alter DNA sequences and modify gene function, has already shown promise in eliminating the genetic coding that drives the development of children's cancer.

The team in Tuesday's study used an enzyme, CRISPR-Cas13b, that binds to relevant RNA sequences on the novel coronavirus and degrades the genome it needs to replicate inside human cells.

Lead author Sharon Lewin from Australia's Peter Doherty Institute for Infection and Immunity told AFP that the team had designed the CRISPR tool to recognize SARS-CoV-2, the virus responsibly for COVID-19.

"Once the virus is recognized, the CRISPR enzyme is activated and chops up the virus," she said.

https://phys.org/news/2021-07-gene-bloc ... human.html

[weatheriscool]

RNA modification may protect against liver disease
https://medicalxpress.com/news/2021-07- ... sease.html
by University of California, Los Angeles

A chemical modification that occurs in some RNA molecules as they carry genetic instructions from DNA to cells' protein-making machinery may offer protection against non-alcoholic fatty liver, a condition that results from a build-up of fat in the liver and can lead to advanced liver disease, according to a new study by UCLA researchers.

The study, conducted in mice, also suggests that this modification—known as m6A, in which a methyl group attaches to an RNA chain—may occur at a different rate in females than it does in males, potentially explaining why females tend to have higher fat content in the liver. The researchers found that without the m6A modification, differences in liver fat content between the sexes were reduced dramatically.

In addition, in a preclinical model, the investigators demonstrated that gene therapy can be used to enhance or add modifications to key RNAs to slow down or reduce the severity of liver disease.