Featured Research

from universities, journals, and other organizations

Cancers Appear In Mice Treated With Adeno-Associated Virus, A Gene Therapy Vector

Date:
September 5, 2001
Source:
Washington University School Of Medicine
Summary:
Studying one type of gene therapy in mice, researchers made an unexpected and unsettling discovery: Six animals eventually developed cancer. The results of the NIH-funded study are described in two scientific reports published in the current issue of the journal Gene Therapy.

St. Louis, — Studying one type of gene therapy in mice, researchers made an unexpected and unsettling discovery: Six animals eventually developed cancer. The results of the NIH-funded study are described in two scientific reports published in the current issue of the journal Gene Therapy.

The research team, headed by Mark S. Sands, Ph.D., an assistant professor of medicine and of genetics at Washington University School of Medicine in St. Louis, used adeno-associated virus (AAV) to insert a human gene into 59 newborn mice. The gene coded for the enzyme beta-glucuronidase, which the mice were unable to produce because their own beta-glucuronidase genes were mutated.

Their condition mimicked Sly's syndrome, one of more than 40 lysosomal storage diseases that in aggregate affect approximately 1 in 5,000 babies. Lysosomes are cellular compartments that dismantle complex molecules into constituent pieces. When one of their enzymes is missing, the large molecules pile up, damaging cells in many tissues.

In these mice, just one injection of the gene-carrying virus raised production of beta-glucuronidase enzyme to functional levels for at least a year. The treated mice gained near-normal amounts of weight, their bones grew to almost normal lengths, and they didn't develop retinal problems.

Therefore, gene therapy just after birth prevented many of the symptoms associated with lysosomal storage disease. When the surviving mice were checked at 18 months of age, three of the five had signs of liver cancer. Examination of additional mice that were either sacrificed or spontaneously died between 8 and 18 months identified three more animals with tumors. None of eight surviving untreated mice had cancer.

Moreover, the researchers have never seen these tumors in the many mice they have treated in other ways for beta-glucuronidase deficiency. The Washington University study was not designed to determine whether AAV might be linked to cancer. It set out to test the long-term efficacy of gene therapy for mice lacking beta-glucuronidase.

Possible explanations for the findings include:

* Gene therapy with the particular recombinant AAV used by Sands' group may cause cancer in mice;

* Gene therapy with AAV may cause cancer in mice if performed during the neonatal period;

* Gene therapy with AAV may cause cancer in mice that lack beta-glucuronidase because these mice are immunocompromised and have other organ problems;

* Gene therapy with AAV may cause cancer in mice if the vector is injected intravenously;

* Overexpression of the human beta-glucuronidase gene in mice may cause cancer, regardless of the vector;

* Gene therapy with AAV may cause cancer in mice;

* The disease MPS VII may predispose these animals to malignancies.

Further studies will be needed to distinguish among these possibilities, the researchers stress. Sands’ group currently is repeating the experiment to determine if the results are reproduceable.

The agent used for gene transfer in these experiments, adeno-associated virus, has been used in human gene-therapy trials. However, those human trials employed a localized method of delivery, rather than the systemic, intravenous approach used in this special mouse model. At the time the tumors were discovered, Washington University investigators informed the U.S. Food and Drug Administration and the National Institutes of Health of their findings. The research was discussed in a public meeting sponsored by NIH’s Recombinant DNA Activity Committee, held March 7 in Rockville, Maryland.

An editorial regarding this research can be found in the August issue of the journal Molecular Therapy. The editorial was written by the journal’s editor-in-chief, Inder M. Verma, Ph.D., professor of genetics at the Salk Institute.

Editor's note: Humans who lack beta-glucuronidase have Sly's syndrome (also called beta-glucuronidase deficiency or mucopolysaccharidosis type VII). They are unable to break down certain large carbohydrates (dermatan sulfate, heparan sulfate and chondroitin sufates) and can have short stature, mental retardation, abnormal facial features and numerous other problems. No patient with Sly's syndrome or other lysosomal storage disease has undergone gene therapy with adeno-associated virus. The clinical trials involving AAV have focused on other diseases, such as cystic fibrosis and hemophilia.


Story Source:

The above story is based on materials provided by Washington University School Of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Washington University School Of Medicine. "Cancers Appear In Mice Treated With Adeno-Associated Virus, A Gene Therapy Vector." ScienceDaily. ScienceDaily, 5 September 2001. <www.sciencedaily.com/releases/2001/09/010905072351.htm>.
Washington University School Of Medicine. (2001, September 5). Cancers Appear In Mice Treated With Adeno-Associated Virus, A Gene Therapy Vector. ScienceDaily. Retrieved September 19, 2014 from www.sciencedaily.com/releases/2001/09/010905072351.htm
Washington University School Of Medicine. "Cancers Appear In Mice Treated With Adeno-Associated Virus, A Gene Therapy Vector." ScienceDaily. www.sciencedaily.com/releases/2001/09/010905072351.htm (accessed September 19, 2014).

Share This



More Plants & Animals News

Friday, September 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Chocolate Museum Opens in Brussels

Chocolate Museum Opens in Brussels

AFP (Sep. 19, 2014) Considered a "national heritage" in Belgium, chocolate now has a new museum in Brussels. In a former chocolate factory, visitors to the permanent exhibition spaces, workshops and tastings can discover derivatives of the cocoa bean. Duration: 01:00 Video provided by AFP
Powered by NewsLook.com
Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com
Jury Delivers Verdict in Salmonella Trial

Jury Delivers Verdict in Salmonella Trial

AP (Sep. 19, 2014) A federal jury has convicted three people in connection with an outbreak of salmonella poisoning five years ago that sickened hundreds of people and was linked to a number of deaths. (Sept. 19) Video provided by AP
Powered by NewsLook.com
Raw: Elephant Undergoes Surgery in Tbilisi Zoo

Raw: Elephant Undergoes Surgery in Tbilisi Zoo

AP (Sep. 18, 2014) Grand the elephant has successfully undergone surgery to remove a portion of infected tusk at Tbilisi Zoo in Georgia. British veterinary surgeons used an electric drill to extract the infected piece. (Sept. 18) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins