Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Halt Spread of HIV with RNAi

11.08.2008
Using a novel method to deliver small molecules called siRNAs into T cells, researchers dramatically suppressed HIV in the first-ever animal model that mirrors progression of the disease in humans. The siRNAs knocked down three key genes and kept the infection from spreading in mice containing human immune cells infected with the virus.

Hopes languished last September when a promising candidate HIV vaccine failed to work. Despite this setback, many researchers still believe immunization is possible, and a new study suggests they’re correct—at least at the cellular level.

Working in mice infected with HIV, a team used a method called RNA interference to knock down three genes in T cells, protecting them from the virus. This method seemed to prevent HIV from jumping between cells in the mice.

“For the first time, we’ve used RNAi to dramatically suppress HIV infection in an organism,” says corresponding author Premlata Shankar, who conducted the work while she was a junior investigator at the Harvard Medical School-affiliated Immune Disease Institute and an assistant professor at Harvard Medical School. Shankar is now a professor at Texas Tech University Health Sciences Center in El Paso.

... more about:
»HIV »HIV vaccine »Harvard »RNA »RNAi »Shankar »T cells »Virus »immunization »siRNA

Although labs must verify the findings in other animal models before attempting clinical trials, this method—published online Aug. 7 in Cell—may eventually supplement or replace the harsh drug cocktails currently prescribed to patients with HIV, reducing the side effects of treatment.

When the Nobel Prize in Physiology or Medicine was awarded in 2006 for the discovery of RNAi, the judges speculated that it might “lead to novel therapies in the future.” Researchers hoped to flood specific cells in patients with short interfering RNAs (siRNAs), molecules that silence genes by disrupting the protein templates they produce. But scientists weren’t sure how to deliver the siRNAs exclusively into relevant cell types within an organism.

In collaboration with Sang-Kyung Lee of Hanyang University, Shankar’s lab overcame this obstacle, delivering siRNAs directly into T cells, which are targeted by HIV. The team used an apparatus analogous to a truck equipped with GPS and a trailer hitch to haul the siRNAs to their destination. The truck—in this case, a single-chain antibody developed by Georg Fey of the University of Erlangen in Germany—homed to a protein found exclusively on the surface of T cells. The trailer hitch—an oligo-9-arginine—pulled siRNAs along for the ride.

This new antibody delivery vehicle lends itself to mass production in a dish. The team built thousands of these carriers for use in experiments, loading them with siRNAs targeting three key genes. One encodes a human protein called CCR5, which dots the surface of T cells and allows HIV to gain entry. The others encode proteins produced by the virus within cells upon infection.

Harvard Medical School postdoctoral researcher and first author Priti Kumar mixed the siRNAs with the antibody carriers and injected them into the veins of mice that harbor human T cells rather than their own. These mice serve as an animal model of HIV. After being infected with the virus, the mice mirror progression of the disease in humans.

Developed by study co-authors Leonard Shultz of the Jackson Laboratory and Dale Greiner of the University of Massachusetts, these mice lack their own immune systems, so they tolerate tissue from other species. The team injected the mice with human blood stem cells, which divided time and again, building a human immune system in their hosts. When infected with HIV, the synthetic immune system seemed to respond as it would in humans, since T cell levels followed the same pattern in both species.

Kumar’s siRNAs halted T cell destruction in the mice, essentially stopping the virus in its tracks.

“Both prophylactic and therapeutic regimens proved successful,” said Kumar. “Apparently, the siRNAs kept HIV from entering most T cells and kept it from replicating when it managed to slip inside.”

Kumar and Shankar caution that labs need to confirm the findings in other animals, tweak the dosage, and tinker with the siRNA delivery vehicle before attempting clinical trials. In addition, the molecules degrade with time, so periodic shots may be necessary to maintain cellular immunity, precluding large-scale vaccination.

“I’m not saying we’ve developed tomorrow’s therapy, but this is a major step forward,” says Shankar. “We’ve used a small animal model for HIV and proven that RNAi works in that model.”

John Rossi, a pioneer in RNA-based therapeutics who was not part of the study, hopes labs will use the new animal model to compare the side effects of potential and existing therapeutic regimens.

“The number one problem with the current antiretroviral drug regimens is toxicity,” says Rossi, a professor at the Beckman Research Institute of the City of Hope. He wonders if siRNAs will eventually enable doctors to lower the doses of existing drugs in patients. Perhaps siRNAs will one day supplement or replace harsh antiretrovirals.

“Overall, I see this work as an exciting proof of principle,” says Rossi. “This is a strategy that can be developed for clinical applications in humans.”

This research is supported by the National Institutes of Health, the Korea Ministry of Education and Science Technology, and the Center for AIDS Research at Harvard.

Alyssa Kneller | Newswise Science News
Further information:
http://hms.harvard.edu

Further reports about: HIV HIV vaccine Harvard RNA RNAi Shankar T cells Virus immunization siRNA

More articles from Life Sciences:

nachricht An ion channel with a doorkeeper: The pH of calcium ions controls ion channel opening
25.06.2019 | Johannes Gutenberg-Universität Mainz

nachricht Symbiotic upcycling: Turning “low value” compounds into biomass
25.06.2019 | Max-Planck-Institut für Marine Mikrobiologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fraunhofer IDMT demonstrates its method for acoustic quality inspection at »Sensor+Test 2019« in Nürnberg

From June 25th to 27th 2019, the Fraunhofer Institute for Digital Media Technology IDMT in Ilmenau (Germany) will be presenting a new solution for acoustic quality inspection allowing contact-free, non-destructive testing of manufactured parts and components. The method which has reached Technology Readiness Level 6 already, is currently being successfully tested in practical use together with a number of industrial partners.

Reducing machine downtime, manufacturing defects, and excessive scrap

Im Focus: Successfully Tested in Praxis: Bidirectional Sensor Technology Optimizes Laser Material Deposition

The quality of additively manufactured components depends not only on the manufacturing process, but also on the inline process control. The process control ensures a reliable coating process because it detects deviations from the target geometry immediately. At LASER World of PHOTONICS 2019, the Fraunhofer Institute for Laser Technology ILT will be demonstrating how well bi-directional sensor technology can already be used for Laser Material Deposition (LMD) in combination with commercial optics at booth A2.431.

Fraunhofer ILT has been developing optical sensor technology specifically for production measurement technology for around 10 years. In particular, its »bd-1«...

Im Focus: The hidden structure of the periodic system

The well-known representation of chemical elements is just one example of how objects can be arranged and classified

The periodic table of elements that most chemistry books depict is only one special case. This tabular overview of the chemical elements, which goes back to...

Im Focus: MPSD team discovers light-induced ferroelectricity in strontium titanate

Light can be used not only to measure materials’ properties, but also to change them. Especially interesting are those cases in which the function of a material can be modified, such as its ability to conduct electricity or to store information in its magnetic state. A team led by Andrea Cavalleri from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg used terahertz frequency light pulses to transform a non-ferroelectric material into a ferroelectric one.

Ferroelectricity is a state in which the constituent lattice “looks” in one specific direction, forming a macroscopic electrical polarisation. The ability to...

Im Focus: Determining the Earth’s gravity field more accurately than ever before

Researchers at TU Graz calculate the most accurate gravity field determination of the Earth using 1.16 billion satellite measurements. This yields valuable knowledge for climate research.

The Earth’s gravity fluctuates from place to place. Geodesists use this phenomenon to observe geodynamic and climatological processes. Using...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on UV LED Technologies & Applications – ICULTA 2020 | Call for Abstracts

24.06.2019 | Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

 
Latest News

For a better climate in the cities: Start-up develops maintenance-free, evergreen moss façades

25.06.2019 | Architecture and Construction

An ion channel with a doorkeeper: The pH of calcium ions controls ion channel opening

25.06.2019 | Life Sciences

Cooling with the sun

25.06.2019 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>