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Immune cells engineered in lab to resist HIV infection, Stanford study shows
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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HP Cabinet Decisions: Eligibility Criteria for BPL List, Special Task Force to Combat Drug Abuse & Other Decisions
Shimla-The Himachal Pradesh Cabinet, in its meeting held on Thursday, approved the inclusion of the following families in the BPL list:
- Families with no adult members between the ages of 18 and 59.
- Women-headed families.
- Families whose head has a disability of 50 per cent or more.
- Families that worked for at least 100 days under MNREGA in the previous financial year.
- Families whose earning members are suffering from chronic diseases such as cancer, Alzheimer’s, Parkinson’s, muscular dystrophy, thalassemia, or any other condition resulting in permanent disability.
The Cabinet also approved the establishment of a Special Task Force to combat drug abuse and dismantle drug trafficking and organized crime networks in the state through a comprehensive and multi-faceted approach.
Additionally, the Cabinet decided to promulgate an ordinance to amend Schedule 1A of the Indian Stamp Act of 1899. This amendment will facilitate the levy of a uniform stamp duty rate of 12 per cent on transfer and lease transactions secured under Section 118(2)(H) of the Himachal Pradesh Tenancy and Land Reforms Act, 1972, with prior approval from the State Government.
The Cabinet approved a ban on the felling of trees, except for Safeda, Poplar, Bamboo, and Khair (for sale), in accordance with a ten-year program.
The Cabinet reiterated its request to the Government of India to adopt a 90:10 funding formula for the power component of the Kishau Multipurpose Project, similar to the formula adopted for its water component. Alternatively, the Cabinet proposed providing a 50-year interest-free loan for the entire amount payable by the State Government for the power component under the Inter-State Agreement.
It approved the establishment of a 1 MW Green Hydrogen Project in Nalagarh, to be executed by HPPCL.
The Cabinet sanctioned the imposition of Green Energy Development Charges for Pumped Storage Projects. A charge of ₹2.5 lakh per MW per year will be levied for the first 10 years after the project’s commissioning, increasing to ₹5 lakh per MW per year thereafter.
Approval was given to introduce the Himachal Pradesh Sadbhawana Legacy Cases Resolution Scheme 2025 to resolve pending cases, litigations, and arrears under subsumed enactments such as VAT, CST, Entry Tax, etc.
The Cabinet decided to designate the area surrounding the Tara Devi Temple in Shimla district as a Green Area.
It approved the creation and filling of 10 Junior Office Assistant (IT) posts for the Himachal Pradesh Public Service Commission, Shimla.
The Cabinet selected the Centre for Development of Advanced Computing (C-DAC), under the Ministry of Electronics and Information Technology, Government of India, to conduct computer-based tests for the recruitment of Group-C posts through the Himachal Pradesh Rajya Chayan Aayog, Hamirpur.
Approval was granted for creating the Block Primary Education Office at Rohnat by bifurcating the existing Block Primary Education Office at Shilai in the Sirmaur district.
The Cabinet decided to transfer three-gram panchayats — Matyal, Kudal, and Dhadol — from Development Block Lambagaon to Development Block Baijnath in Kangra district to serve the residents of these areas better.
The Cabinet approved the Baddi-Barotiwala-Nalagarh Development Authority Land Pooling Policy-2025.
It also approved the establishment of the Himachal Pradesh State Water Informatics Centre to collect data from domain-specific bodies, develop new databases, and disseminate comprehensive water-related information.
Shimla– Himachal Pradesh Government has initiated action against Zila Parishad cadre employees, who have been on strike since September 30 over their demands for a merger with the Panchayati Raj Department. To start with, the Govt has terminated the services of 167 Junior Engineers (JEs) and ordered fresh recruitment of Diploma or Degree holders in Civil Engineering.
According to the Director, Panchayati Raj Department, Rugved Milind Thakur, notifications have been issued to the Chief Executive Officers of Zila Parishad and the Deputy Commissioners regarding the same.
Earlier, Chief Minister Sukhvinder Singh Sukhu, in a statement to the media, had said that at a time when the State was hit by a natural disaster and is in the middle of carrying out relief work and rehabilitation of the affected people was not an appropriate time for such strike. He further added that the demands of these Zila Parishad employees would be attended to when conditions are suitable. He had added that the employees wouldn’t get anywhere by using pressure tactics against the State Government.
The Panchayati Raj and Rural Development Minister Anirudh Singh had maintained the same argument and urged the employees to end the strike and get back to work because their absence was obstructing relief work. Anirudh Singh argued that the HP Government was serious about the demands of the employees, but their merger will have to go through various stages in accordance with the rules and legal procedure. This process would take time, he said. However, the Minister also failed to convince the striking employees to get back to work.
A few days back, a spokesperson of the HP Panchayati Raj Department had issued a statement, which said,
“Absence of technical staff was causing delayed wage payment to the MGNREGS workers as well as hampering development works being undertaken for disaster relief and restoration. A special package has been announced by the state government for the disaster-affected families. Under this package, reconstruction of houses and cowsheds and other relief and rehabilitation works, conservation activities of agriculture and horticulture land, etc. were to be done. But these works are being affected due to the absence of technical staff.”
The Department had also sought details from all the Chief Executive Officers of the Zila Parishads regarding the absence of employees in view of the delay in developmental and disaster relief works by October 18, 2023. The government termed their absence as unauthorized.
The Department said that it was taking all necessary steps to deal with the situation arising due to the absence of certain categories of employees.
“There should not be any unnecessary delay in disaster relief and rehabilitation works and the Panchayati Raj Department was determined to ensure all assistance and other benefits to the affected families on time,” the Spokesperson said in a statement.
The Department had also handed over the charge of Panchayat Secretaries temporarily to Gram Rozgar Sevaks, Sewing Teachers, and Panchayat Chowkidars. They were also given financial powers. The Panchayati Raj Department justified that these alternative arrangements were helping to restore the issuance of certificates and other routine works of the Gram Panchayats.
However, the striking employees on Friday said the alternative arrangements weren’t working at all, thus, causing a huge inconvenience to the people. The employees said that the decision of the government to sack the JEs has not affected their strike, and it will go on indefinitely till their demand for merger is met.
Why Zila Parishad Employees Are on A Strike
4,700 Zila Parishad cadre employees have been on indefinite pen-down strike since September 30, stalling the routine functions of Zila Parishads. The main demand of the Zila Parishad cadre employees is the merger with the Panchayati Raj Department so that they could avail benefits on a par with the employees of the other government departments.
These employees also said that despite a poll promise before the elections to the State Assembly, the current Congress government was denying them the new pay scale.
These employees argued that they were suffering financial loss, and they were not receiving dearness allowance (DA) and arrears while other employees were getting these benefits.
The employees are also demanding regularization under the contract policy. The strike has also received support from Panchayat representatives.
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HP Cabinet Decisions: Construction in Shimla’s Green Belt Areas Permitted, Special Relief Package Approved
Shimla-Himachal Pradesh Cabinet on Wednesday held a meeting under the Chairmanship of Chief Minister Thakur Sukhvinder Singh Sukhu. Here are the decisions taken by the Cabinet:
Approval to Construction in Shimla’s Green Belt Areas
The Cabinet also decided to amend the Shimla Development Plan and construction would be permitted in green belt area lying above the road, from Navbahar to Ram Chandra Chowk to Machhiwali Kothi to Christ Church to Lakkar Bazar to IGMC to Sanjauli Chowk to Navbhar where there are no trees.
As per the Government, residential construction in the Green Belt area as per the Shimla Development Plan will be permitted only on those plots in which there are no trees.
It also decided to amend HP Town and Country Planning Rules to allow construction at a distance of 5 meters and 7 meters from Nallah and khad respectively.
The Cabinet decided to provide two Biswas of land in urban areas and three Biswas of land in rural areas who have been rendered homeless and those who are not left with land suitable for the construction of new houses.
HP Govt’s Special Package Approved
Nod was given a Special Relief Package for the disaster-affected families in the State as announced on 30th September 2023 by Chief Minister Sukhvinder Singh Sukhu.Under the Special Package:
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- The compensation of Rs. 1.30 lakh for a completely damaged house would be increased five and a half times to Rs. 7 lakh.
- The compensation of Rs. 4,000 for partial damage to a ‘kutcha’ house would be increased by 25 times to Rs. 1 lakh, while the compensation for partial damage to a ‘pucca’ house to be increased by 15 and a half times, from Rs 6500 to Rs. 1 lakh.
- Compensation of Rs. 25,000 given in case of damage to a shop or dhaba would also be enhanced four times to rupees one lakh.
- The HP Government will also provide increased financial assistance of Rs. 50 thousand instead of Rs. 3000 for damage to the cowshed. T
- The state government will provide assistance of Rs. 50 thousand for damage or loss to the belongings of the tenants thereby marking a 20 times increase, from the existing Rs. 2500.
- For the loss of large milch and draught animals compensation of Rs. 55000 and for goat, pig, sheep and lamb Rs. 6000 per animal compensation would be provided.
- The compensation of Rs. 3615 per bigha for damage to agricultural and horticultural land would be increased to Rs. 10 thousand.
- The compensation on crop loss of Rs. 500 per bigha is to be increased eight times to Rs.4000.
- The financial assistance for removing silt from agricultural and horticultural land is to be enhanced from Rs. 1384.61 per bigha to Rs. 5000.
This special package would be granted from 24th June 2023 to 30th September 2023.
‘Van Mitra’ Scheme Approved
The Cabinet approved the Forest Department ‘Van Mitra’ Scheme. Under this scheme, one ‘Van Mitra’ each, in 2061 Forest Beats would be engaged. It also decided to fill up 100 vacant posts of Forest Guards in the Forest Department on a contractual basis.
It decided to enhance the honorarium of Jal Rakshaks, Multi-Purpose Workers, para fitters and para pump operators of Jal Shakti Vibhag by Rs. 500 per month raising it to Rs. 5000, Rs. 4400, Rs. 6000 and Rs. 6000 respectively.
Chintpurni Passenger Ropeway
The Cabinet approved in principle to establish a passenger ropeway system from Chintpurni Baba Mai Dass Bhawan Parking to Chintpurni Temple in PPP mode in district Una with a cost of Rs. 76.50 crore.
It also gave its approval to hire 15 e-taxis in the Transport Department.
It decided to promote Amateur and Community Radios for ‘Alternate Communication during emergencies in all districts of the State. This would provide effective information exchange between information sources, emergency managers and those impacted by disaster or emergent situations.
The Cabinet decided to reduce the Additional Goods Tax on lead by 25 paise per kg.
It also accorded approval to grant 234 routes for private operators and additional 100 routes for tempo travelers to provide better transport facilities to the people of the State.
It also gave its approval for declaring Traffic Inspectors, Motor Vehicles Inspectors, Senior Motor Vehicle Inspectors of the Transport department and Assistant Sub Inspector and Head Constable of the Police Department as designed authority to compound the offences under various Sections of the Motor Vehicle Act, 1988.
HP Cabinet Decisions: Eligibility Criteria for BPL List, Special Task Force to Combat Drug Abuse & Other Decisions
HP Govt Takes Action Against Striking Zila Parishad Employees, Orders Fresh Recruitment
HP Cabinet Decisions: Construction in Shimla’s Green Belt Areas Permitted, Special Relief Package Approved
Himachal Aims to be India’s First Green Energy State by 2025
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