In gene therapy, the delivery vehicles used are viruses since they are designed not to damage the cell when they reach there, but not considering how the virus makes their exit from the cell could have consequences.
To help in attaching viruses to the cells, some viruses use heparan sulfate which is a molecule. Since the molecule is found in several kinds of cells, even those of the animal tissue, a new study in the journal Virology discovered that it tends to prevent the virus from escaping.
An associate professor of biological science at Purdue University, David Sanders, said that it might not be necessarily a good thing that the virus is not being released. Sanders further claimed that it could have its consequences on stimulating the immune system.
Sanders said, "As we're engineering viruses more and more to do gene transfer and gene therapy, one thing we need to be taking into account is their ability to exit the cell."
The new technique that uses genes and doesn't rely on drugs or surgery to treat a disorder is known as gene therapy. There are few ways gene therapy can be done such as putting a disease-inducing gene with a healthy copy of the gene, taking out a mutated gene that malfunctions, or initiating an entirely new gene that can assist the body in the fight against the disease.
The viruses used in gene delivery are set up not to cause disease in a new host, but it is hard to tell whether there will be unintended consequences of a virus never leaving the cell.
The associate professor further maintained that the potential usefulness of heparan sulfate is not to have the protein search for the cell's receptor in three-dimensional space; instead, it draws the protein to the surface.
When the protein gets to the surface, it makes the search two-dimensional. But with the introduction of their virus into the cell that produces heparan sulfate, it cannot escape.
When they invade the DNAell, retroviruses, such as HIV, insert a copy of their genome into it. And retroviruses work well for gene transfer since they are permanently incorporated into the generic material of the host cell.
Sanders and team then created a viral pseudotype, a retrovirus that resembles an alphavirus from outside, in an attempt to generate a virus that enhances the insertion of DNA into cells with heparan sulfate on their surfaces.
Next, the team altered the alphavirus protein that was predicted to make the pseudotyped virus utilizing heparan sulfate for entry.
When the result came out, they discovered that instead of creating a better virus, they end up finding no virus. This consequence is due to the interaction between the protein they modified and the heparan sulfate already in the cell; the protein was being retained there.
Since there is an increasing rate of viruses as delivery vehicles, researchers need to put high consideration on the tools they use to facilitate entry could hamper the exit.
