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Immune cells engineered in lab to resist HIV infection, Stanford study shows

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Researchers at the Stanford University School of Medicine have found a novel way to engineer key cells of the immune system so they remain resistant to infection with HIV, the virus that causes AIDS.

A new study describes the use of a kind of molecular scissors to cut and paste a series of HIV-resistant genes into T cells, specialized immune cells targeted by the AIDS virus. The genome editing was made in a gene that the virus uses to gain entry into the cell. By inactivating a receptor gene and inserting additional anti-HIV genes, the virus was blocked from entering the cells, thus preventing it from destroying the immune system, said Matthew Porteus, MD, an associate professor of pediatrics at Stanford and a pediatric hematologist/oncologist at Lucile Packard Children’s Hospital.

“We inactivated one of the receptors that HIV uses to gain entry and added new genes to protect against HIV, so we have multiple layers of protection — what we call stacking,” said Porteus, the study’s principal investigator. “We can use this strategy to make cells that are resistant to both major types of HIV.”

He said the new approach, a form of tailored gene therapy, could ultimately replace drug treatment, in which patients have to take multiple medications daily to keep the virus in check and prevent the potentially fatal infections wrought by AIDS. The work was done in the laboratory, and clinical trials would still be needed to determine whether the approach would work as a therapy.

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“Providing an infected person with resistant T cells would not cure their viral infection,” said Sara Sawyer, PhD, assistant professor of molecular genetics and microbiology at the University of Texas-Austin and a co-author of the study. “However, it would provide them with a protected set of T cells that would ward off the immune collapse that typically gives rise to AIDS.”

The study was published in the Jan. 22 issue of Molecular Therapy.

One of the big challenges in treating AIDS is that the virus is notorious for mutating, so patients must be treated with a cocktail of drugs — known as highly active antiretroviral therapy or HAART — which hit it at various stages of the replication process. The researchers were able to get around that problem with a new, multi-pronged genetic attack that blocks HIV on several fronts. Essentially, they hope to mimic HAART through genetic manipulation.

The technique hinges on the fact that the virus typically enters T cells by latching onto one of two surface proteins known as CCR5 and CXCR4. Some of the latest drugs now used in treatment work by interfering with these receptors’ activity. A small number of people carry a mutation in CCR5 that makes them naturally resistant to HIV. One AIDS patient with leukemia, now famously known as the Berlin patient, was cured of HIV when he received a bone marrow transplant from a donor who had the resistant CCR5 gene.

Scientists at Sangamo BioSciences in Richmond, Calif., have developed a technique using a protein that recognizes and binds to the CCR5 receptor gene, genetically modifying it to mimic the naturally resistant version. The technique uses a zinc finger nuclease, a protein that can break up pieces of DNA, to effectively inactivate the receptor gene. The company is now testing its CCR5-resistant genes in phase-1 and -2 trials with AIDS patients at the University of Pennsylvania.

The Stanford scientists used a similar approach but with an added twist. They used the same nuclease to zero in on an undamaged section of the CCR5 receptor’s DNA. They created a break in the sequence and, in a feat of genetic editing, pasted in three genes known to confer resistance to HIV, Porteus said. This technique of placing several useful genes at a particular site is known as “stacking.”

Incorporating the three resistant genes helped shield the cells from HIV entry via both the CCR5 and CXCR4 receptors. The disabling of the CCR5 gene by the nuclease, as well as the addition of the anti-HIV genes, created multiple layers of protection.

Blocking HIV infection through both the CCR5 and CXCR4 receptors is important, Porteus said, as it hasn’t been achieved before by genome editing. To test the T cells’ protective abilities, the scientists created versions in which they inserted one, two and all three of the genes and then exposed the T cells to HIV.

Though the T cells with the single- and double-gene modifications were somewhat protected against an onslaught of HIV, the triplets were by far the most resistant to infection. These triplet cells had more than 1,200-fold protection against HIV carrying the CCR5 receptor and more than 1,700-fold protection against those with the CXCR4 receptor, the researchers reported. The T cells that hadn’t been altered succumbed to infection with 25 days.

Porteus said he views the work as an important step forward in developing a gene therapy for HIV.

“I’m very excited about what’s happened already,” he said. “This is a significant improvement in that first-generation application.”

He said a potential drawback of the strategy is that while the nuclease is designed to create a break in one spot, it could possibly cause a break elsewhere, leading to cancer or other cell aberration. He said it’s also possible the cells may not tolerate the genetic change.

“It’s possible the cells won’t like the proteins they’re asked to express, so they won’t grow,” he said.

But he said he believes both problems are technically surmountable. He said the researchers’ next step is to test the strategy in T cells taken from AIDS patients, and then move on to animal testing. He said he hopes to begin clinical trials within three to five years.

Though the method is labor-intensive, requiring a tailored approach for each patient, it would save patients from a lifelong dependence on antiretroviral drugs, which have adverse side effects, Porteus noted.

He said he also hopes to adapt these techniques for use against other diseases, such as sickle cell anemia, one of his areas of interest. Porteus works with patients in the Pediatric Bone Marrow Transplant service at Packard Children’s.

In addition to Sawyer, he collaborated with Richard Voit, a former Stanford graduate student who is now an MD/PhD candidate at the University of Texas Southwestern Medical Center, and Moira McMahon, PhD, a former postdoctoral scholar at Stanford who is now at the University of California-San Diego.

The study was supported by a grant from the American Foundation for AIDS Research and by a Laurie Krauss Lacob Faculty Scholar Award from the Lucile Packard Foundation for Children’s Health.

Information about Stanford’s Department of Pediatrics, which also supported the work, is available at http://pediatrics.stanford.edu.

BY RUTHANN RICHTER

Source: Stanford School of Medicin

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Himachal Heads Towards Full Lockdown as Covid Cases Spike; 5,424 New Infections and 37 Deaths Reported in 24 Hours

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Shimla-With 37 fatalities reported in the last 24 hours due to severe Covid symptoms, Himachal Pradesh’s total death toll has climbed to 1,817 on Saturday. The state reported 5,424 new cases of infection taking the total to 1,28,330.

Kangra district reported the highest number of fatalities with 14 deaths followed by state capital Shimla that reported 11 deaths in the last 24-hours. A 27-year-old woman was the youngest patient to die due to coronavirus and Pneumonia in the district of Kangra.

The infection has claimed the lives of 497 people in Kangra and 391 in Shimla till now.

 A total of 18725 people across the state were sampled for the infection on Saturday, an increase from Friday when 12,930. On Saturday a total of 3,634 tests remain awaited, the maximum is from Kangra district with 1,258 Covid tests awaited.

View the District-wise Details of all COVID-19 Cases for May 8, 2021 (Till 7 pm) Below:

According to a report by The Tribune, many RT-PCR test samples collected in Kangra district on April 29 were still awaited. Considering the fatality of the virus this mismanagement by state health authorities can prove deadly for many patients if they do not receive the diagnosis on time. With a delay of over a week, patients are also doubting the authenticity of the samples since they are potent for testing for just 24 hours under ideal conditions.

Meanwhile, the Indian Medical Association came down heavily on the Health Ministry on Saturday criticising the lack of medical equipment and crumbling medical infrastructure. In a press release on Saturday, the IMA urged the central government to ‘wake up from its slumber’ as thousands of Covid patients succumbed to severe symptoms due to lack of basic medical equipment like oxygen cylinders, ambulances, and more. The IMA also pointed out the lack of Covid vaccine stock even though everyone above the age of 18 is eligible to receive their shots. The press release also mentioned that sporadic night curfew will not be much effective in curbing the spread of infection and requested the government that life is more precious than the economy.

The Himachal government has now planned on imposing a full lockdown in the state considering the rapid increase of infection cases.  However, the government is apprehensive in using the term “lockdown” and is still calling it “corona curfew”.

Also Read: Curfew Rules in Himachal to Change from May 10, More Restrictions to be Imposed

The update comes after a partial corona curfew was put in place from May 7. Under the new lockdown rules, public transport both private and the government will not be running, and shops selling essential commodities will remain open for three hours only. Timing of the shops would be fixed by the concerned Deputy Commissioners. Citizens will also not be allowed to travel in private vehicles unless there is an urgent requirement.

View the District-wise Details of all COVID-19 Cases for May 8, 2021 (Till 7 pm) Below:

Covid-19 deaths in himachal pradesh may 8

Feature Photo:Image by fernando zhiminaicela from Pixabay

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Curfew Rules in Himachal to Change from May 10, More Restrictions to be Imposed

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HP Govt new curfew rules in himachal pradesh

Shimla-Curfew Rules in Himachal Pradesh have been changed from 10 May onwards. More stringent restrictive measures would be put in place, the state government said today.

The Disaster Management Cell of the Revenue Department, HP Government, today issued a notification regarding the changes in the curfew rules which will come into effect from May 10 (6 am) to 17 May (6 am).

According to the notification, from 10 May onwards all public and private transport would remain closed. Movement of private vehicles would also be restricted except for emergency cases, vaccination, testing and treatment for COVID-19, and those used in the delivery of essential, medical and public services.  

Only shops selling essentials and daily needs such as food grains, fruits, vegetables, dairy products, meat and fish, animal feed, fodder, seeds, fertilizers and pesticides, groceries would be allowed to open for only three hours.

Further, shops dealing in construction material would also remain closed for now.

This time limit would not apply to pharmacies and medical stores.

Notification regarding the timings would be issued by the concerned district administrations, the government said.   

The reason behind the decision was cited to be the alarming rate of COVID-19 spread and fatality. The situation is likely to become more like a complete lockdown. 

The decision has also come after Chief Minister Jairam Thakur spoke to Prime Minister Narender Modi regarding the situation in the state.

It’s pertinent to mention that the state government had been facing flak over imposing a corona curfew with very flexible rules. Chief Minister, however, argues that the decision was taken to ensure that the livelihood of the people doesn’t get affected adversely.

Also Read: IMA Asks Govt, Why Are We Hiding the Actual Death Count? Demands Health Ministry to Wake Up from Slumber

Also, today, the Indian Medical Association issued a statement in which it condemned the union health ministry over its lackadaisical attitude in handling the COVID-19 pandemic in a stern tone. The Association lashed out at the government over ignoring its recommendation for a complete and nationwide lockdown to break the chain.

Also, the Association alleged that the ministry is deciding without taking ground realities into account, which the health experts had been bringing to its notice. The IMA also questions the government as to why it was trying to hide the true number of COVID-19 casualties.

Today, the state has lost 37 lives to the infection and reported 5424 new cases.

Chief Minister claims that the state has a sufficient supply of oxygen, but the number of available oxygen cylinders was still an issue that needs to be attended to.

Earlier today, the government suggested that more stringent restrictive actions could be taken in Sirmaur, Solan, Una, and Kangra district, which are reporting a high number of new cases and fatalities.

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Himachal Reports 56 Coronavirus Deaths in 24 Hours, Over 60% Had No Comorbidities

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Shimla– On Friday Himachal Pradesh reported 56 deaths due to coronavirus infection taking the total number of casualties in the state to 1,780, according to official data released by the state government. This is the highest number of deaths in a day in the state so far. About 38 patients (over 60%) who succumbed to the infection had no other medical condition.

A total of 4,177 new cases of coronavirus infection were reported on Friday taking the total to 1,22,906.

In Kangra district, a total of 21 Covid-patients succumbed to the severe symptoms, reporting the highest number of casualties. Meanwhile, Sirmaur reported nine casualties followed by Solan district where eight patients died due to the infection.

The youngest patient who died of Covid-19 was a 20-year-old woman from the Mandi district. The patient was also reported to have comorbid pulmonary tuberculosis. One of the patients who died due to severe symptoms of Covid-19 was a 27-year-old woman from Sirmaur district who was pregnant with her second child.

Also Read: Coronavirus Claims Life of 12-Year-Old Boy in Himachal 

Today, a total of 15,495 samples were tested as compared to yesterday’s 18694. The state government had been directing officials to increase testing regularly, but the actual number hasn’t crossed 20,000 per day so far.

View the District-wise Details of all COVID-19 Cases for May 7, 2021 (Till 7 pm) Below:

corona cases in himachal

A total of 122,930 people across the state have been sampled for coronavirus till now. Out of this test results of 5,234 people are awaited while.

After Backlash, HP Govt Increases Incentive for Health Staff

On Thursday, the state government decided to increase the incentive paid to the final year students from MBBS, nursing, and contractual doctors in Covid hospitals who will be roped in to boost the on-ground staff.

Earlier, the state government had announced that it will be paying Rs 3,000 per month to the Junior and Senior Resident doctors and fourth and fifth-year medical students while final year nursing students were to be paid Rs 1,500 per month for their duty in Covid wards. After facing much criticism, the state government has now increased the incentive to Rs 10,000 per month for fourth and fifth-year MBBS students, Junior and Senior Residents, and Contractual Doctors. For third-year Nursing students, the incentive has been increased to Rs 6,000, while Contractual Lab staff, and third-year General Nursing and Midwifery students will get Rs 5000 per month for their Covid duty.

View the District-wise Details of all COVID-19 Casualties for May 7, 2021 (Till 7 pm) Below:

COVID-19 report himachal pradesh 2021 l

hp govt covid-19 data may 2021

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