Holds promise for vaccine, drug development
Knocking out the KU80 gene in Toxoplasma gondii has made the human parasite an effective model to help understand its entire parasite family, according to researchers at Dartmouth Medical School. The development holds promise for the creation of new therapies and vaccines, the lead researcher told PFQ.
"KU80 knockouts can now be used to efficiently produce gene knockouts and gene replacements for the identification of drug targets, vaccine candidates, and characterization of virulence factors," said David J. Bzik, PhD, a professor of microbiology and immunology at Dartmouth.
T. gondii and its relatives, the virulent parasites Plasmodium, which causes malaria, and Cryptosporidium, which causes diarrhea, have been a challenge to researchers because of their unusual method of gene repair, according to Dr. Bzik. While in most organisms a gene can be knocked out and replaced in the same spot to change or determine its function, in T. gondii the repair mechanism replaces genes randomly. This has made it difficult to identify and isolate strains with genetic modifications. The KU80 knockout eliminates this problem, he said.
"KU80 knockouts of T. gondii exhibit a high percentage of homologous recombination and eliminate the major bottleneck to genetic manipulation and engineering biology of the Apicomplexan parasite," Dr. Bzik said in an e-mail to PFQ. "KU80 knockout strains now enable rapid, reliable, and precisely defined genetic modification of T. gondii."
The development holds promise for therapies beyond the immediate parasite family, Dr. Bzik said.
"Several naturally evolved biological properties of the T. gondii vaccine platform make this technology a potentially superior platform for the development of therapeutics and vaccines against infectious diseases, cancer, and other human diseases," he said.