Connect with us

Misc News/Press Release

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

Misc News/Press Release

Himachal Reports 87 COVID-19 Deaths in 11 Days With a Steep Rise in Cases

Published

on

COVID-19 deaths in Himachal pradesh on november 10

Shimla-With nine more COVID-19 deaths on Wednesday, the tally for Himachal Pradesh has jumped to 399. The state is witnessing a surge in November as 87 deaths were reported during the last 11 days. Yesterday’s fatalities included seven males and two females aged between 45 to 87 years. Find the reasons for these fatalities below:

himachal pradesh -Update on covid-19 deaths

Further, according to the state Health Department’s official statistics, 610 new cases of COVID-19 were detected yesterday, of which Shimla reported highest (118) cases, followed by Mandi (116).

In Mandi district, as many as 26 more teachers and some students reportedly tested positive yesterday. The infected also included two doctors of Tanda Medical College, Kangra, and a couple of policemen in Sakoh.

Operation theatre at the Kamala Nehru Hospital, Shimla, was reportedly closed for a week. Similarly, the women police station in Shimla was also closed following the detection of a case.

Further, the state High Court has taken suo moto cognizance of a news report published in an English daily and issued a notice to the government. The news pertained to Indira Gandhi Medical College, which ran out of space for COVID-19 patients in isolation wards.

As per official data, the total for COVID-19 in the state had reached 27418 till yesterday evening (9 pm), of which 5605 were active cases. Mandi district has reported highest 4194 cases, followed by Solan (3958), Shimla (3725), and Kangra (3635).

The state government is barely speaking on the alarming rise in fatalities and its strategy to control it. But Chief Minister, while addressing a public meeting at Sihunta under Bhatiyat Assembly Constituency yesterday, did hail the Prime Minister and claimed that the nation is out of COVID-19 crisis.

“He (PM) has successfully brought the Nation out of Covid-19 crisis,”

Chief Minister said.

HP Health Department COVID-19 Bulletin for November 11, 2020 (9 pm)

 

 

Continue Reading

Misc News/Press Release

Himachal Reports 12 COVID-19 Deaths in Single Day, Surge in Cases in Shimla

Published

on

Himachal Pradesh COVID-19 deaths till diwali

Shimla-COVID-19 continues to wreak havoc in Himachal Pradesh as a record 12 fatalities were reported on Tuesday. Of the 611 new positive cases yesterday, Shimla reported highest 148 with seven fatalities. The deceased included 11 males and a female aged between 47 to 92 years.  During the last three days, the state has reported 25 fatalities. Find the details regarding the causes of deaths below:

Himachal Pradesh Record COVID-19 deaths

The state government had yesterday decided to close all educational institutes in Himachal for 15 days after over a hundred teachers and students tested positive in schools. The government termed it as a special vocation for students, teachers, and non-teaching staff of all educational institutes.

The capital has witnessed a surge as over 750 cases were reported during the last six days. In the season of festivity and marriages, social distancing and other guidelines issued by the MHA for personal protection are being flaunted, which is only fueling the spread. 

On top of it, the COVID-19 Hospitals in the state have begun to run out of beds for patients in isolation wards. The largest medical facility in the state – Indira Gandhi Medical College & Hospital- was packed to its full capacity, which was only 85 beds. Dr Rajneesh Pathania, Principal of IGMC, confirmed the report. According to media reports, DDU hospital, Shimla, had also run out of space. The government is yet to prepare the make-shift hospitals it had announced a couple of months ago. 

So far, according to the official statistics, the state had reported a total of 26808 cases till yesterday evening (9 pm), and the official COVID-19 death tally had mounted to 390.

HP Health Department COVID-19 Bulletin for November 9, 2020 (9 pm)

Update Himachal Pradesh COVID-19 for november 10, 2020

Featured Image: [email protected]

 

Continue Reading

Misc News/Press Release

Amid Alarming Surge in COVID-19 Cases and Deaths, Hospitals Including IGMC Running Out of Space

Published

on

covid-19 in himachal pradesh igmc beds full

Shimla– Amid the festive season, Himachal Pradesh is witnessing an alarming surge in COVID-19 cases and fatalities. As a matter of huge concern, the Indira Gandhi Medical College & Hospital, Shimla, has run out of beds in isolation facility and can’t accommodate more patient, unless someone is discharged or dies. There was space for only 85 patients at the hospital, which is full presently.

The DDU hospital, too, is running out of capacity with a surge in cases. Further, make-shift hospitals announced by the state government haven’t seen light of day. IGMC is the largest medical facility of the state and COVID-19 patients in critical condition were referred here.  

The situation could worsen due to the ongoing festive and wedding season. Markets are crowded and people are hardly following social distancing norms in marriages.

Further, yesterday seven people including a 16-year-old girl lost their lives. The decision to open schools seems to be backfiring as hundreds of teachers and several students were found positive for COVID-19 during the past few days. There are speculations that the state government could decide on closing schools for some time in the Cabinet meeting to be held today.

Details regarding the causes of fatalities below:

Himachal Pradesh COVID-19 deaths in november 2020 f

On Monday, five doctors and nine staff nurses at the Shri Lal Bahadur Shastri Government Medical College and Hospital, Nerchowk in Mandi district, tested positive.

Yesterday, the state reported a record 711 confirmed cases with seven fatalities in a single day. Shimla district reported the highest 204 confirmed cases.

The COVID-19 death tally has now mounted to 378, while the total number of cases had reached 26197 till yesterday evening (till 9 pm).

HP Health Department COVID-19 Bulletin for November 9, 2020 (9 pm)

 

Himachal Pradesh covid-19 cases on november 10

Continue Reading

Trending