CHAPEL HILL, N.C. -- Molecular doorways on the surface of cells may be important factors in the success or failure of human gene therapy using altered viruses, according to researchers at the University of North Carolina at Chapel Hill.
A report of their study published Jan. 4 in the journal Nature Medicine applies directly to a promising gene therapy method in which a harmless, genetically engineered virus called AAV (adeno-associated virus) is used to deliver genes into the body. The new findings tell us that the entry of AAV into the cell is facilitated by surface receptor molecules called alpha V beta 5-integrins. Without the presence of these integrins, the ability of AAV to "infect" the cell and deliver its genetic payload is diminished, say study authors led by Candace Summerford, doctoral student in pharmacology at the UNC-CH School of Medicine.
"We have been able to show that the virus interacts with two receptors: a primary receptor, which serves as an attachment molecule, and a secondary receptor -- the integrin co-factor -- that facilitates virus internalization," Summerford says. She notes that AAV is yet another example of a virus that uses multiple cell surface receptors to mediate its entry into cells. HIV, herpes simplex, and adenovirus, a cold virus, also employ multiple receptors.
The UNC-CH researchers tested hamster cell lines lacking the alpha-v
beta5 integrin. Attempts at getting AAV into these cells proved far more
difficult than those on cells that were genetically altered to express the
integrin. "In the absence of integrin, the virus sits on the outside of the
cell," says Dr. R. Jude Samulski, study senior author and director of the
UNC-CH Gene Therapy Center. He points to micro-photographs of the virus glowing
fluorescent red on the cell's surface. "This is the same cell where the integrin
has been put in," Samulski says. He then refers to the next image in which the
fluorescence is gone fr
Contact: Lynn Wooten
University of North Carolina at Chapel Hill