Newly identified receptor may help gene therapy go viral

January 28, 2016 by Bruce Goldman, Stanford University, Stanford University
Credit: NIH

Gene therapy, whereby a patient's disorder is treated by inserting a new gene, replacing a defective one, or disabling a harmful one, suffered a setback in 1999, when Jesse Gelsinger, an 18-year-old with a genetic liver disease, died from immense inflammatory complications four days after receiving gene therapy for his condition during a clinical trial. It was quite a while before clinical trials in gene therapy resumed.

But what Stanford virologist Jan Carette, PhD, describes as "intense interest" in the field is once again in full bloom. Gene therapies for several inherited genetic disorders have been approved in Europe, and a gene-therapy approach for countering congenital blindness is close to approval in the United States.

That a virologist would be paying such close attention to this topic isn't odd, as the most well-worked-out method for introducing genetic material to involves the use of a domesticated virus.

If there's one thing viruses are really good at, it's infecting cells. Another viral trick is transferring their genes into cellular DNA—it's part of their modus operandi: hijacking cells' replicative machinery and diverting it to production of numerous copies of themselves. Scientists have become increasingly adept at taming viruses, tweaking them so they retain their ability to infect cells and insert genes, but no longer contain factors that wreck tissues or taunt the infected victim's immune system into a rage destructive to virus and victim alike.

Adenovirus-associated virus—ubiquitous in people and not associated with any disease – makes a great workhorse. Properly bioengineered, it can infect all kinds of cells without replicating itself inside of them or triggering much of an immune response, instead obediently depositing medically relevant genes into the to repair a patient's defective metabolic, enzymatic, or synthetic pathways.

Figuring out how to tailor this viral servant so it will invade cells more efficiently, or invade some kinds of cells and tissues but not others, would broaden gene therapy's utility and appeal. In a series of experiments described in a study in Nature, Carette's group, with collaborators from Oregon Health & Science University and the Netherlands, used a sophisticated method pioneered by Carette to bring that capability a step closer.

A virus can attach itself to a target cell by latching onto a molecule embedded in that cell's surface. In the case of adenovirus-associated virus, that viral-receptor molecule is already known. (The molecule obviously is there for some constructive purpose, which doesn't stop the invading virus from taking advantage of the mutual attraction.) Simply glomming on to the cell's surface isn't enough, though. To get to the all-important nucleus, where the genetic jewelry is ensconced, the virus has to penetrate the cell as well. Until now, the molecule on which adenovirus-associated virus hops a ride downtown was anybody's guess.

In the new study, Carette and his colleagues identified, in human , precisely that transport molecule. This discovery could lead to ways of raising or lowering the molecule's expression in different tissues so that therapeutic genes get delivered to their intended addresses, and nowhere else.

Explore further: Study could help improve gene therapy for heart disease, cancer

More information: S. Pillay et al. An essential receptor for adeno-associated virus infection, Nature (2016). DOI: 10.1038/nature16465

Related Stories

Study could help improve gene therapy for heart disease, cancer

October 12, 2011
A Loyola University Chicago Stritch School of Medicine study could lead to improved gene therapies for conditions such as heart disease and cancer as well as more effective vaccines for tuberculosis, malaria and other diseases.

Human genomic pathways to bronchitis virus therapy

November 18, 2015
Viral replication and spread throughout a host organism employs many proteins, but the process is not very well understood. Scientists at A*STAR have led a collaborative study to learn which host factors play a key role in ...

Viral infections leave a signature on human immune system, study finds

December 15, 2015
A team of immunologists and informatics experts at the Stanford University School of Medicine has identified a distinctive pattern of gene expression that distinguishes people with a viral infection from those with a bacterial ...

Researchers identify way to increase gene therapy success

October 30, 2013
Scientists in The Research Institute at Nationwide Children's Hospital have found a way to overcome one of the biggest obstacles to using viruses to deliver therapeutic genes: how to keep the immune system from neutralizing ...

Recommended for you

Cold can activate body's 'good' fat at a cellular level, study finds

March 21, 2018
Lower temperatures can activate the body's 'good' fat formation at a cellular level, a new study led by academics at The University of Nottingham has found.

Switch discovered to convert blood vessels to blood stem cells in embryonic development

March 20, 2018
A switch has been discovered that instructs blood vessel cells to become blood stem cells during embryonic development in mice. Using single-cell technology, researchers from the Wellcome Sanger Institute in Cambridge and ...

Scientists discover new causes of cellular decline in prematurely aging kids

March 19, 2018
In a recent paper published in Cell Reports, Saint Louis University researchers have uncovered new answers about why cells rapidly age in children with a rare and fatal disease. The data points to cellular replication stress ...

Don't blame adolescent social behavior on hormones

March 19, 2018
Reproductive hormones that develop during puberty are not responsible for changes in social behavior that occur during adolescence, according to the results of a newly published study by a University at Buffalo researcher.

Stem cells treat macular degeneration

March 19, 2018
In July 2015, 86-year-old Douglas Waters developed severe age-related macular degeneration (AMD). He struggled to see things clearly, even when up close.

Measuring neutrophil motility could lead to accurate sepsis diagnosis

March 19, 2018
A microfluidic device developed by Massachusetts General Hospital (MGH) investigators may help solve a significant and persistent challenge in medicine—diagnosing the life-threatening complication of sepsis. In their paper ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Jan 28, 2016
Are those duty bound Viral Servants enticed by providing any entertainment for them? ...such as a Go Game or a virtual reality gadget?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.