A promising approach to gene therapy involves short DNA fragments (interfering RNA) that bind to specific genes and block their "translation" into the corresponding, disease-related protein. A stumbling block has been the efficient and targeted delivery of RNA into the cells. Researchers led by Hongjie Dai at Stanford University have chosen to use carbon nanotubes as their "means of transport".
This has allowed them to successfully introduce RNA fragments that "switch off" the genes for special HIV-specific receptors and co-receptors on the cells’ surface into human T-cells and primary blood cells. This leaves few "entry hatches" for the HIV viruses. The researchers report in the journal Angewandte Chemie that this allows for much better silencing effect to the cells than current transport systems based on liposomes.
T-cells are one of the types of white blood cells important for a good immune defense; they detect and destroy virus-affected cells. However, they themselves are among the targets attacked by HIV. In order to enter into a T-cell, the virus must first dock to a receptor known as CD4. Also involved is the co-receptor CXCR4. The use of short interfering RNA strands allows the CD4 and CXCR4 genes of the T-cell to be shut off. The T-cell then strops producing these receptors and the virus cannot find any points of attack on the surface of the cell. This could significantly slow down an HIV infection, as previous work have shown.
But how to get the RNA fragments into the T-cells? The shells of nonpathogenic viruses can be used to smuggle genetic material into cells, but this is dangerous in therapeutic applications because they can trigger allergies. Liposomes, tiny bubbles of fat, are safe but have proven to be ineffective for use in T-cells. Dai and his co-workers have tested a new transport system: carbon nanotubes are known for their abilities to be absorbed by cells and to smuggle other molecules in at the same time. The researchers attached phospholipids—molecules from which cell membranes are also made—to chains of polyethylene glycol. The phospholipids nestle securely onto the outer wall of the carbon nanotubes while the polyethylene glycol chains protrude into the surrounding solution. The required RNA molecules were fastened to the ends of these chains. Once inside the cell, the RNA could easily be split off by means of a sulfur–sulfur bridge.
Citation: Hongjie Dai, siRNA Delivery into Human T Cells and Primary Cells with Carbon-Nanotube Transporters, Angewandte Chemie International Edition 2007, 46, No. 12, doi: 10.1002/anie.200604295
Source: John Wiley & Sons, Inc.
Related stories:
Study of dark-skinned mice leads to protein linked to bone marrow failure in humans
The study of dark-skinned mice has led to a surprising finding about a common protein involved in tumor suppression, report researchers at the Stanford University School of Medicine. The results may lead to new treatments for bone marrow failure in humans.
Class of antibiotics can enhance gene-silencing tool
A way to turn off one gene at a time has earned acceptance in biology laboratories over the last decade. Doctors envision the technique, called RNA interference, as a tool to treat a variety of diseases if it can be adapted to humans.
Researchers Discover Remnant of an Ancient 'RNA World'
(PhysOrg.com) -- Some bacterial cells can swim, morph into new forms and even become dangerously virulent - all without initial involvement of DNA. Yale University researchers describe Friday in the journal
Science how bacteria accomplish this amazing feat - and in doing so provide a glimpse of what the earliest forms of life on Earth may have looked like.
Improved culture system for hepatitis C virus infection
A University of California, San Diego School of Medicine researcher has developed the first tissue culture of normal, human liver cells that can model infection with the Hepatitis C virus (HCV) and provide a realistic environment to evaluate possible treatments. The novel cell line, described in the July 16 issue of
PLoS ONE, will allow pharmaceutical companies to effectively test new drug candidates or possible vaccines for the HCV infection, which afflicts about 170 million people worldwide. Currently, there is no animal model that is effective for testing such therapies.
A new look at how genes unfold to enable their expression
(PhysOrg.com) -- Cornell researchers have uncovered surprising new information about the process by which genes are unwrapped and exposed so that they can be expressed.
Detecting flu viruses in remote areas of the world
Researchers in Ohio and New Mexico are reporting an advance in the quest for a fast, sensitive test to detect flu viruses — one that requires no refrigeration and can be used in remote areas of the world where new flu viruses often emerge. Their new method, the first to use sugar molecules rather than antibodies, is in the July 2 issue of the
Journal of the American Chemical Society.
Researchers Engineer Self-Destructing Virus
University of Arizona researchers have sown the seeds of a virus' destruction in its own genetic code – or rather, in the genetic code of the organisms it seeks to infect. Their work could improve both the understanding of how viruses work as well as the ability to make plants and animals more virus-resistant.
Researchers discover mechanism that explains how cancer enzyme winds up on ends of chromosomes
Human cancer cells divide and conquer. Unless physicians can control that division with surgery, chemotherapy or radiation, the wildly dividing cells will eventually destroy a person's life.