Connect with us

News

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

Published

on

Researchers-at-the-Stanford-University-School-of-Medicine-have-found-

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.

RELATED NEWS

» Top AIDS scientist delivers Stanford lecture, declaring end in sight for pandemic
“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

News

Shimla, Manali Receive Season’s First Spell of Snow, Cheers Tourism Industry

Published

on

snowfall in shimla 2021

Shimla-First spell of snow in Shimla’s tourist destinations, Narkanda and Kufri, has cheered the tourism industry as it would increase the footfall of tourists. Similarly, higher parts of Manali also reported a light spell of snow on Sunday evening. Lahaul-Spiti, however, reportedly witnessed heavy snowfall and Atal Tunnel, Rohtang, was closed for traffic. Parts of the Kinnaur district also recorded a spell of snow.

Chopal in Shimla had received 2-3 inches of snow, while Dodra Kwar recorded one foot of snow, according to the Met Department.

In Kullu, Jalori Pass had received 3 inches of snow, Rohtang top 2.5 feet, and Atal Tunnel 1.5 feet.

In Lahaul-Spiti, Koksar/Sissu had recorded 18 inches of snow, Keylong 8 inches, Darcha 12 inches, Udaipur 4 inches, Tindi 2 inches, Kaza 1 inch, and Lossar 2 inches of snow.

In Kinnaur, Chitkul had recorded 15.4 cms of snow, Kalpa 5 cms, and Sangla 7.62 cms. Nichar also received a light spell.

This change in weather has triggered a cold wave across the state. Further, the Himachal Pradesh Meteorological Department had issued a yellow alert for December 5, 2021. The Met has predicted rain and snow on December 6 too. While the weather is predicted to be dry on December 8, the state could witness more rain and snow on December 7 and December 9, according to the Met Department.

Most roads, except in Lahaul-Spiti, remain open to traffic movement, the district administrations of Shimla and Kullu confirmed. Further, the administrations said preparations are being made to keep the roads clear in case of heavy snowfall.

This tourist season is crucial for the hospitality industry which was worst hit by the pandemic induced restrictions. However, the entry of Omicron – the new variant of Covid-19 that has been termed as a variant of concern by the WHO-haunts the season. India had reported as many as 21 cases of Omicron till Sunday. If the HP Government decides to impose restrictions on the entry of the domestic tourist in view of the spread of the new variant, the hospitality industry could again face losses.  

Continue Reading

News

Himachal Achieves 100% Vaccination Target, OPD at AIIMS, Bilaspur, Inaugurated   

Published

on

vaccination second dose in himachal pradesh

Shimla-Himachal Pradesh has achieved the 100 percent target of the second dose of Covid vaccination, the State government informed on Sunday.  Himachal Pradesh has become the first State of the country in achieving the target of cent per cent vaccination of targeted eligible age group, it informed.  

According to the HP Government, all eligible 53,86,393 adults have been administered the second dose of the vaccine.

District-Wise Vaccination Details

District

Number of People Vaccinated 

Bilaspur  318150
Chamba 352605
Hamirpur 361954
Kangra 1140439
Kinnaur 68460
Kullu 322643
Lahaul-Spiti 25494
Mandi 738818
Shimla 634019
Sirmaru 410187
Solan 584326
Una 429298

A complete vaccination was performed first in the inaccessible areas and tribal areas of the state and Kinnaur district became the first district in the entire country to administer the second dose of the vaccine to all eligible adults, the government informed.

On this occasion, Jagat Prakash Nadda, the Member of Parliament and National BJP President, also addressed a felicitation ceremony of Covid Vaccination Workers at Bilaspur on Sunday.

Nadda also dedicated the first OPD at AIIMS Kothipura in Bilaspur. The AIIMS Bilaspur would be made fully functional within the next six months, said Nadda.

 

jp nadda at aiims bilaspur

JP Nadda at AIIMS Bilaspur

He said that the foundation stone of this institution was laid about three years back and it would have been completed a year ago, but the pace was affected due to the corona pandemic. He said that Himachal Pradesh has got an Rs. 500 crore Satellite centre of PGI Chandigarh at Una.

He also congratulated the State Government, doctors, health care workers and all the frontline workers for achieving this unique feat. 

Union Minister of Health, Chemicals and Fertilizers Mansukh Mandaviya, Chief Minister Jai Ram Thakur and Union Minister of Information and Broadcasting, Youth Affairs and Sports Anurag Singh were also present on the occasion

 

Continue Reading

News

Himachal Records Fresh Spell of Snow, HP Met Issues Alert

Published

on

snowfall in himachal pradesh

Shimla-The weather in Himachal Pradesh has taken a turn with a prediction of rain and snowfall till December 5, 2021. At the time of writing this report, Kaza in Lahaul-Spiti was receiving a fresh spell of snow, cheering the tourists, as well as, the hoteliers. So far, the traffic movement was normal in the region.

This has caused a sharp drop in temperatures across the state.

The District Administration of Lahaul-Spiti has advised the locals and tourists to avoid wandering to high altitude areas unnecessarily.

The HP Meteorological Department, Shimla, has also issued a yellow alert for December 2 and December 5. While the plains can experience light to moderate rainfall at a few places,  the middle and higher hills could witness widespread rain and snow on December 2.   

For December 4, the HP Met had predicted light to moderate rain across the state. For December 5, however, the Met has issued an yellow alert with a prediction of rain and snow at several places.

Continue Reading

Trending