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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-

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

Misc News/Press Release

Himachal: 10 COVID-19 Deaths in Single Day Take Tally to 145, DDU MS Replaced Following Patient Suicide

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Shimla-DDU covid-19 patient suicide 2

Shimla-Himachal Pradesh reported 10 COVID-19 deaths on September 24, 2020, which took the state’s death tally to 145. This is the biggest single-day-spike in the fatalities – a matter of huge worry amid community spread. Kangra district reported the highest six deaths while Shimla, Chamba,  Sirmaur, and Kullu reported one death each. The deceased including eight males and two females were aged between 55-78 years. At least five of these deceased were patients of diabetes mellitus.So far,

So far,  Kangra district has reported the highest 37 deaths, followed by Shimla (24), Solan (23), Mandi (20), Una (10), Sirmaur (10), Chamba (8), Hamirpur (6), Kullu (5), Bilaspur (1), and Kinnaur (1).

Go through the reasons of deaths given by the state Health Department below:Himachal pradesh corona deaths Sept 24

According to the official update, 337 new positive cases were registered yesterday. The total for the state has now reached 13,386. (Scroll down to view statistics for all districts)

DDU MS Replaced After COVID-19 Patient Suicide 

As part of the damage control, the Medical Superintendent of Shimla’s Deen Dayal Upadhyay (DDU) Hospital, Lokender Sharma, was replaced after a COVID-19 patient committed suicide inside the hospital premises. Dr Ramesh Chauhan has been appointed as the new MS.  The case has led to protests against poor facilities and mismanagement in COVID-19 hospitals in the state. The opposition even staged a protest on September 5.

Reacting to his removal, Dr Lokender denied any negligence on his part and said he had been working with insufficient staff and limited facilities. He also alleged that the administration did not consider his repeated complaint regarding the same. Himachal Pradesh Medical Officers Association (HMOA) has also pointed out that the state government has not done anything to chalk out a comprehensive strategy to deal with the pandemic. They also pointed out the lack of trained staff.

These developments, including a sudden spurt in the fatality rate among COVID-19 patients, are now exposing the poor preparedness of the state government. The government doesn’t seem to have any clue about controlling the spread. There is no data on the projected number of actual cases as it is not possible to trace all infected amid a community spread.

While there is a dire need to make more efforts to save lives, the government and the Chief Minister Jairam Thakur appear to be busy in preparing for the visit of the Prime Minister Narender Modi for the opening of the Rohtang Tunnel.

HP Health Department COVID-19 Bulletin- September 24, 2020 (9 PM)

DDU COVID Patient suicide in himachal pradesh

Feature Photo: [email protected]

 

 

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Five More COVID-19 Deaths, Three Suicides, Shimla’s Kotkhai Nagar Panchayat Sealed

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shimla kotkhai nagar panchayat sealed

Shimla– Five more COVID-19 casualties were reported in Himachal Pradesh on September 23, 2020. According to the official update from the Health Department, a total of 280 cases were reported till 9:00 pm today . The COVID-19 death tally is rising at an alarming rate with the onset of a community spread. Currently, a total of 135 persons have lost their lives due to COVID-19.(Scroll down for district-wise statistics)

These deaths were reported from Solan (1), Kangra (2), and Mandi (2). The deceased aged between 58 years to 77. Read the reasons for deaths below:

Shimla- kotkhai nagar panchayat sealed

Kotkhai Nagar Panchayat Sealed for Four Days

Kotkhai Nagar panchayat of Shimal district was sealed today after four persons tested positive at the CHC, Kotkhai. However, there is one case which has increased worries for both the people and the administration.

According to the BMO, Kotkhai, one of these persons, identified as Kavinder Kanwar, runs a car parking at the Kotkhai Bazaar. He also runs a newspaper distribution agency in the same area and deals in mobile recharge business. He frequently handles keys of cars parked in the parking as part of his routine task, it was informed.

“It is quite possible that the concerned positive person has also surely visited several shops and public places in Kotkhai bazaar during the last four days. In this situation, it is difficult to find out the exact contact tracing history due to which there is a high risk of surface transmission and risk of a direct contact person to person,”

informed the Sub-Divisional Magistrate, Theog, in a notification issued today.   

Therefore, the administration has declared the entire Kotkhai Nagar panchayat as containment zone and sealed it except for essential services for four days (till September 27th).

The local police have been directed to restrict any entry to or exit from the area. The BMO has been asked to undertake contact tracing and the Secretary of the Nagar panchayat area has been directed to sanitize the entire area.   

COVID-19 Positive Woman Ends Life at DDU, Shimla

A woman, who was tested positive for COVID-19, and was admitted to the DDU hospital, Shimla, ended her life on the intervening night of September 22-23. The exact reason for the suicide was yet to be ascertained.

Further, two suicides in Kangra district have been associated with the financial distress caused by the COVID-19 pandemic. One of the deceased worked at a fuel station.  The second person was a cab driver. According to the English daily, The Tribune, he had recently received a notice from the bank over non-payment of his loan that he had taken to buy a cab. These suicides are indicators that the people are in dire need of relief from the state government. 

HP Health Department COVID-19 Bulletin- September 23, 2020 (9 PM)

Himachal Pradesh COVID-19 Fatalities on september 23

 

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13 More COVID-19 Deaths in 2 Days, Total Mounts to 130

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Himachal Pradesh COVID-19 update for september 22, 2020

The COVID-19 fatality rate in Himachal Pradesh is on the rise as the death tally reaches 130 with 13 new deaths in the last two days. According to the Health Department’s official COVID-19 Bulletins, State reported seven deaths on September 21 and six on September 22. 

Today, the state registered 331 new confirmed cases with which the COVID-19 tally for the state rose to 12769. Of this total, 4124 are active cases, 8491 have recovered, and 20 migrated to outside the state. The infected also include Nachan MLA Vinod Kumar.

Details of COVID-19 Casualties on Sept 21-22

details of COVID-19 deaths in Himachal pradesh

Today, the highest cases were reported from Sirmaur district (79), followed by Mandi (66), Shimla 48, and Solan 38, and Kullu (25). (Scroll down to view more district-wise statistics.)
However, the actual number of cases could be higher as the state is in the community spread phase. No projection regarding the actual number of cases and deaths has been issued by the state government.

So far, the state government has tested only 271449 persons for COVID-19. Considering the community spread, the state government is supposed to increase the number of tests.

Meanwhile, Chief Minister Jairam Thakur said that people should refrain from going to crowded places and take all precautions. However, tourists thronging the state are hardly following any rules. After lifting all restrictions on inter-state movement, the state government is now preparing to open the inter-state bus services, which would fuel the community spread.  The people are already expressing their resentment with the decision to suddenly lift all restrictions on movement of tourists. Amid these uncertain circumstances, rising fatality rate is the main concern. 

HP Health Department COVID-19 Bulletin- September 12, 2020 (9 PM)

  

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