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Articles » NIAID Scientists Explore Genetic Solutions To Insect-Borne Diseases, NIAID Fact Sheet: NIAID

NIAID Scientists Explore Genetic Solutions To Insect-Borne Diseases, NIAID Fact Sheet: NIAID

Article title: NIAID Scientists Explore Genetic Solutions To Insect-Borne Diseases, NIAID Fact Sheet: NIAID

Conditions: Insect-Borne Diseases, plague, Dengue

Source: NIAID

June 11, 1996

NIAID Scientists Explore Genetic Solutions To Insect-Borne Diseases

By shuttling bubonic plague bacteria from infected rats to humans, the lowly flea helped usher in the Black Death, the infamous pandemic that killed one-fourth of Europe's population during the 14th century. Although plague itself has subsided significantly as a global health problem, blood-sucking insects and the pathogenic organisms they carry continue to afflict populations worldwide. Mosquitoes are the worst offender, with malaria and other mosquito-borne diseases killing millions of people each year.

Conventional methods for controlling insect-borne diseases have thus far met with little long-term success. Preventive vaccines are unavailable, and pathogens and insects commonly develop resistance to drugs and insecticides, respectively. In a fundamentally different approach to this problem, scientists now are using genetic techniques to modify insects in ways that make them incapable of transmitting disease-causing organisms. Although much work remains before these efforts yield practical solutions, researchers supported by the National Institute of Allergy and Infectious Diseases (NIAID) have reported promising findings.

Scientists at Colorado State University recently produced mosquitoes that were unable to transmit the virus that causes dengue fever, a disease that affects tens of millions of people a year in more than 100 countries. A research team that included Ken Olson, Ph.D., Steve Higgs, Ph.D., and NIAID grantees Barry J. Beaty, Ph.D., Carol D. Blair, Ph.D., and Jonathan O. Carlson, Ph.D., injected mosquitoes with dengue virus and with a viral vector that had been genetically engineered to produce a molecule that blocks replication of the dengue virus. Mosquitoes in a control group were co-injected with dengue and a viral vector that lacked the replication-blocking molecule. Eleven days later, no dengue virus could be detected in mosquitoes that received the replication-blocking molecule. Control mosquitoes, on the other hand, produced large quantities of virus and their saliva was able to infect other mosquitoes.

Despite their success, the researchers acknowledge that better gene delivery systems are needed for this strategy to become a practical tool for controlling insect-borne diseases. Dr. Olson and his colleagues used Sindbis, a virus that naturally infects mosquitoes, to transport the dengue replication-blocking molecule. Although the Sindbis vector worked as it was designed to, these disease-controlling modifications are not passed on to subsequent generations. The vector did not transform the mosquitoes, that is, insert the genetic changes that blocked replication of the virus into the mosquitoes' sperm and egg cells.

"Ultimately, mosquito genomes will need to be manipulated with DNA-based transformation techniques to ensure both heritability and transcriptional control of the desired anti-virus agent in the mosquito," the researchers note in their report.

Other NIAID-funded researchers are actively working on efficient genetic transformation systems for mosquitoes. Some are looking at a broad class of DNA molecules known as transposons, unique genetic sequences that are able to jump from one genomic site to another. For more than a decade, scientists have genetically manipulated fruit flies by attaching genes to transposons that then insert themselves, and the attached genes, into the fruit flies' chromosomes. Hugh M. Robertson, Ph.D., an NIAID grantee at the University of Illinois Urbana-Champaign, is trying to identify transposons that could serve as transformation systems for medically important insects.

A key area of research focuses on identifying the disease-controlling genes that vectors could insert into mosquitoes and other insects. Just as the Colorado State researchers were able to insert the gene for a molecule that blocked dengue virus replication, genes that interfere with other pathogens must be found. NIAID grantee Leonard Munstermann, Ph.D., and his colleagues at Yale University are trying to find genes in sand flies that block their ability to transmit leishmaniasis, an often disabling disease that affects 12 million people worldwide.

At the University of Wisconsin, NIAID-funded researchers led by Bruce Christensen, Ph.D., are searching for the genes that allow certain species of mosquito to resist infection with the parasites that cause malaria and filariasis, a lymphatic disease that affects 100 million people in India and Africa. The researchers have found that at least two different genes control mosquito resistance to these parasites. In addition to introducing these anti-parasite traits into mosquitoes, Dr. Christensen and his colleagues hope to harness other mosquito immune responses. One example would be to genetically manipulate defensins, immune molecules in mosquitoes that are switched on by invading bacteria, but not by parasites.

A related research problem concerns getting the vector and its pathogen-controlling genes into the insect embryo so that transformation can take place. Louis H. Miller, M.D., chief of NIAID's Laboratory of Parasitic Diseases, notes that although genetic transformation of mosquitoes has been achieved by microinjecting DNA into individual mosquito embryos, the process is difficult and transformation rates are very low. Dr. Miller and other NIAID intramural investigators have demonstrated that biolistic techniques, in which DNA-coated gold microparticles are shot into insect eggs, can insert DNA into many embryos at a single time, and therefore may be a better way to introduce genes into the mosquito germ line.

NIAID, a component of the National Institutes of Health, supports research on AIDS, tuberculosis and other infectious diseases as well as allergies and immunology.

Prepared by:
Office of Communications and Public Liaison
National Institute of Allergy and Infectious Diseases
National Institutes of Health
Bethesda, MD 20892

Public Health Service
U.S. Department of Health and Human Services


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