Enzyme delivered in smaller package protects cells from radiation damage

Jun 01, 2007

A University of Pittsburgh School of Medicine research team, collaborating with scientists from Stanford University, have developed a new, smaller gene therapy vector that may be effective in delivering a radioprotective enzyme systemically throughout the body which may spare healthy tissue the long-term consequences of therapeutic irradiation. These results are being presented at the 10th annual meeting of the American Society of Gene Therapy, being held May 30 to June 3 at the Washington State Convention & Trade Center, Seattle.

Combined with intensive chemotherapy, high dose whole-body irradiation often is given to patients with blood and lymphatic cancers to wipe out their bone marrow cells prior to subsequent transplantation of hematopoietic stem cells, bone marrow stem cells or peripheral blood progenitor stem cells. However, there is increasing concern that such high doses of radiation may have long-term negative effects on healthy tissues and organs, such as the kidney, liver and thyroid gland.

Based on previous studies showing that intravenous gene therapy delivery of the enzyme manganese superoxide dismutase (MnSOD) could protect mice from whole body irradiation, and in preparation for a potential clinical trial of systemic MnSOD in humans, the University of Pittsburgh and Stanford researchers, led by Joel S. Greenberger, M.D., professor and chair of the department of radiation oncology, University of Pittsburgh School of Medicine, delivered the human MnSOD enzyme into mouse hematopoietic progenitor cells using a newly constructed gene therapy vector called a "minicircle" plasmid.

To determine if the cells transfected with the MnSOD minicircle plasmid retained radioprotective capacity, they irradiated those cells as well as another cell line transfected with MnSOD in a full-sized plasmid. They also irradiated a parent mouse cell line that had not been transfected with MnSOD. After irradiation, the cells were plated in a growth medium and incubated at body temperature for 7 days at which time colonies of greater than 50 cells were counted.

The MnSOD transfected cells were significantly more resistant to ionizing radiation than the non-tranfected cells. However, there was no significant difference in survival between MnSOD-minicircle and MnSOD full plasmid transfected cells. According to Dr. Greenberger, whose group is currently conducting a phase I/II clinical trial in lung cancer patients consisting of twice-weekly swallowed MnSOD for protection of the esophagus from chemoradiotherapy damage, these results suggest that minicircle DNA containing the human MnSOD transgene confers undiminished radioprotection to cells.

"Because we now can deliver MnSOD in this very small vector, we will be able to get this radioprotective enzyme more efficiently into all of the cells of the body and give patients receiving total body radiation for systemic cancers better long-term outcomes. This also has implications for the prophylactic protection of those who may be the first responders to a nuclear accident or a terrorist attack, such as a "dirty bomb," he explained.

Source: University of Pittsburgh Schools of the Health Sciences

Explore further: What are the chances that your dad isn't your dad?

add to favorites email to friend print save as pdf

Related Stories

Protein related to aging holds breast cancer clues

Jan 27, 2011

The most common type of breast cancer in older women -- estrogen and progesterone receptor (ER/PR) positive breast cancer -- has been linked to a protein that fends off aging-related cellular damage.

Recommended for you

Obese British man in court fight for surgery

Jul 11, 2011

A British man weighing 22 stone (139 kilograms, 306 pounds) launched a court appeal Monday against a decision to refuse him state-funded obesity surgery because he is not fat enough.

2008 crisis spurred rise in suicides in Europe

Jul 08, 2011

The financial crisis that began to hit Europe in mid-2008 reversed a steady, years-long fall in suicides among people of working age, according to a letter published on Friday by The Lancet.

New food labels dished up to keep Europe healthy

Jul 06, 2011

A groundbreaking deal on compulsory new food labels Wednesday is set to give Europeans clear information on the nutritional and energy content of products, as well as country of origin.

Overweight men have poorer sperm count

Jul 04, 2011

Overweight or obese men, like their female counterparts, have a lower chance of becoming a parent, according to a comparison of sperm quality presented at a European fertility meeting Monday.

User comments : 0

More news stories

Down's chromosome cause genome-wide disruption

The extra copy of Chromosome 21 that causes Down's syndrome throws a spanner into the workings of all the other chromosomes as well, said a study published Wednesday that surprised its authors.

Progress in the fight against quantum dissipation

(Phys.org) —Scientists at Yale have confirmed a 50-year-old, previously untested theoretical prediction in physics and improved the energy storage time of a quantum switch by several orders of magnitude. ...

Meteorites yield clues to Martian early atmosphere

(Phys.org) —Geologists who analyzed 40 meteorites that fell to Earth from Mars unlocked secrets of the Martian atmosphere hidden in the chemical signatures of these ancient rocks. Their study, published ...