Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Researchers Halt Spread of HIV with RNAi

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:

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

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>