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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

Campus Watch

Include Yoga as Compulsory Subject in Himachal’s Schools, Demands HPYSA

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Yoga as Compulsory Subject in Himachal Schools

Shimla-Himachal Pradesh Yogasana Sports Association (HPYSA), Chairman, Prof. GD Sharma, has urged the State Government to include Yoga as a compulsory subject at the school level and to teach it in colleges as well. While addressing a press conference very recently, he said that Yoga has been recognized as a sport by the government of India and sports quota in jobs will now apply to Yoga players.

GD Sharma said the inclusion of Yoga at schools and college would open new avenues for the youth as a career. He said that HPYSA has launched a statewide drive to connect youth in the Hill state with Yoga. It’s all set to organize the first online State level Yogasana Contest in March and winners, thereof, will participate in the national championship to be held from March 24 to 26.

HPYSA is affiliated with the National Yogasana Sports Association, a body recognized by the central ministry of youth affairs and sports, he added.

Sharma, a former professor of HP University, has been instrumental in promoting Yoga across the globe when he was posted in Indonesia by the government of India with a diplomat status from 1992 to 1997 

He said HPYSA will make all efforts to create job opportunities for youth through Yoga.

About Recognition of Yogasana as a Competitive Sport.

On December 17, 2020, the Ministry of AYUSH and Ministry of Youth Affairs and Sports had announced the formal recognition of Yogasana as a competitive sport.

The Government of India had said that Yogasana is an integral and important component of Yoga, which is psycho-physical in nature and popular across the globe for its efficacy in fitness and general wellness.

It had further added , “Yogasana becoming a sport will also ensure new technologies and new strategies being inducted into the disciplines, to benefit our athletes and officials towards building fruitful and fulfilling careers in this field”.

The government had also said that it was planning to include Yogasana as a Sport discipline in Khelo India and in the University Games and we will also pitch it at the National Games and in Olympics.

The AYUSH ministry had said that the sports discipline of Yogasana is likely to have 51 medals in 4 events & 7 categories. The proposed events for both men and women include Traditional Yogasana, Artistic Yogasana (Single), Artistic Yogasana (Pair), Rhythmic Yogasana (Pair), Free Flow/Group Yogasana, Individual All Round – Championship and Team Championship.

According to the AYUSH, following steps or activities will form part of the road map and the future development of Yogasana Sport:

  1. A pilot Yogasana Competition named as “National Individual Yogasana Sports Championship (Virtual Mode) to be held in early 2021.
  2. Launching of an Annual Calendar of competitions, events and programs of Yogasana sport.
  3. Development of Automated Scoring System for the Yogasana Championship.
  4. Courses for Coaches, Referees, Judges and Directors of competitions.
  5. Coaching camps for players.
  6. Launch of a League of Yogasana, to ensure a career and social status for performers, experts and practitioners, to create Sports Stars among Yogasana athletes.
  7. To introduce Yogasana as a Sport discipline in National Games, Khelo India and international sports events.
  8. Steps to create job opportunities for Yogasana athletes.

 

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Himachal Pradesh: Today Last Chance for First Dose of COVID-19 Vaccine for Left-Out Health Care Workers

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Himachal Pradesh last date for first dose of covid-19 vaccine

Shimla-Mission Director National Health Mission, Himachal Pradesh, Dr. Nipun Jindal yesterday informed that 25th February 2021 will be the last date of the mop-up round for the vaccination of Health Care Workers (HCWs).

All the Chief Medical Officers were directed to prepare the list of all such Health Care Workers who are registered on CoWIN portal but have not been vaccinated for the first dose till date. Districts have been directed to create sessions for all such left out beneficiaries as per the requirement to ensure maximum coverage of Health Care Workers.

All the CMOs were further directed to analyse and review their block-wise coverage to assess the left-out beneficiaries and to further direct their Block Medical Officers to arrange sessions in all the blocks. It was also reiterated to utilize all available channels of communication to reach out to the left-out beneficiaries.

Dr. Nipun Jindal further informed that this will be the last chance for all HCWs to get the first dose of the COVID vaccine. He appealed to all registered but not vaccinated health care workers for reporting to their nearest session site on 25th February for getting vaccinated irrespective of receiving SMS for the session scheduling. Such beneficiaries will be scheduled on-site.

He further informed that till now more than 78 percent of registered Health Care Workers have been vaccinated in the State. So far only 0.5 percent AEFI cases have been reported, of which only one needed hospitalization.

He further appealed to the beneficiaries to ignore any rumours and come forward to get themselves vaccinated as the vaccine is completely safe.

Dr. Jindal also informed that Himachal Pradesh is the leading state in the country in 2nd dose coverage of Health Care Workers, achieving more than 91 percent of the expected target.

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HP Govt Notifies New Paragliding, River Rafting Sites, Plans Floating Restaurant at Tattapani

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HP Govt notified new adventure sports sites in himachal pradesh

Shimla-New sites for adventure sports activities in Himachal Pradesh has been notified by the State Government, informed Director Tourism and Civil Aviation, Yunus Khan, yesterday.

On 23 February the State Government had announced that it was planning to open a floating restaurant at Tattapani in Mandi district. Chief Minister Jai Ram Thakur had also inaugurated water sports activities at Tattapani from Shimla.

Additional sites for paragliding and river rafting has been notified. Now tourists visiting the state could experience paragliding at new sites in the districts of Kullu, Kangra, Mandi, Chamba, and Shimla.

New notified paragliding sites in Himachal Pradesh include:

  1. Pandhara to Gadsa and Khargan to Nangabag in district Kullu
  2. Tang Narwana to Khirku  in Kangra district
  3. Darouta to Lahra (Khajjiar) and Lahra to Darol and Raina to Nainikhad Jarei in Chamba district
  4. Prashar and Spenidhar in Mandi district
  5. Tikkar, Junga  to Chauri/Junga in Shimla district

New site for river rafting on river Beas from Nadaun to Dehra Bridge has also been notified. 

Other than the notified river rafting sites, already existing sites in Himachal includes

  1. Shamshi to Jehri and Babeli to Pirdi in Kullu district,
  2. Luhri to Tattapani in Shimla district,
  3. Darch to Jispa and Kaza Bridge to Tabo in Lahaul-Spiti. 

He said that for the safety of paragliding pilots and tourists, the Department of Tourism in collaboration with Atal Bihari Vajpayee Institute of Mountaineering & Allied Sports (ABVIMAS), Manali, has taken the initiative to provide training courses to paragliding pilots, which includes SIV course, a safety training course for Tandem paragliding pilots.

Director said that in the last two years an expenditure of approximately rupees two crore has been incurred on imparting training courses to 749 persons, which includes basic mountaineering course, paragliding course, basic, intermediate and advance skiing course including SIV course for providing training to locals from these newly identified areas.

In addition to these new notified sites, there are many other notified sites in Himachal Pradesh for paragliding for adventure enthusiasts. These sites include

  1. Bir-Billing, Chohla Indru Nag near Dharamshala in Kangra district,
  2. Solang Nalah, Marhi, Talaiti-Talogi, Majach-Shanag in Kullu district
  3. Mauja Rehad to Karganoo in Solan district
  4. Ser Jagaas in Sirmaur district.

State Government had already also notified H.P. Miscellaneous Adventure Activities ‘Amendment’ Rules. The government also said that it would start new water sports activities like a speed boat, water skiing, jet skiing, ski-boarding, water scooter, cruise etc. in various water bodies.

In the Karsog area, the Government had said, popular tourist destinations such as Mahunag Temple, Kamaksha Temple etc. would be developed from a religious tourism point of view. 

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