BOSTON, Mass., June 5--Viruses are normally all together too good at entering our cells. But when scientists alter them to carry desirable genes for genetic therapy, they usually have difficulty getting into the cells where their cargo is needed. Harvard Medical School researchers seem to have overcome this obstacle by building these weighty, less pugnacious viruses a bridge.
The new technique links the virus and target cells by a bridge consisting of two proteins?the growth factor EGF and the receptor for a protein found on the avian leukosis virus (ALV). When applied to cultured cells, the protein bridge allowed the virus not only to bind but also enter the designated cell targets. The researchers report these findings in the June 9 Proceedings of the National Academy of Sciences.
"The novel thing here is that this delivery device works efficiently, which allows for the first time the possibility that we can use this approach to target any cell type we want," says John Young, associate professor of microbiology and molecular genetics. He developed the method in collaboration with graduate student Sophie Snitkovsky.
Most efforts to design in vivo gene delivery systems have focused on further modifying the virus, for example, by building into its envelope a structure that directs the virus to a specific cell type. But the tinkering appears to interfere with the ability of the virus to enter the cells.
"We wanted to find an approach where we could preserve as much as possible the normal virus envelope -cell receptor interaction," says Young. He and Snitkovsky created the EGF-ALV receptor protein bridge and applied it to a series of cell types, including one with the normal EGF receptor and one without. Only those cells with the EGF receptor bound the molecular bridge.
To see if the virus, once linked, could actually enter cells, the
researchers introduced a gene conferring resistance to the antibiotic neomyc
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Contact: Peta Gillyatt
pgillyat@warren.med.harvard.edu
617-432-0443
Harvard Medical School
9-Jun-1998