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Dendrimers deliver the goods to tackle virus infection


03 November 2008

A dendrimer that delivers antibodies into cells has potential for infectious disease treatment, say US scientists. Eva Harth, Peter Wright and colleagues, of Vanderbilt University, Nashville, developed the macromolecular antibody carriers to treat virus-infected cells. 

Respiratory syncytial virus infected cells displaying green fluorescence

RSV infected cells display green fluorescence which weakens when the cells are treated with dendrimer-antibody conjugate

In the body, antibodies identify foreign objects such as viruses so that they can be recognised by the immune system. Harth used an antibody specific for the respiratory syncytial virus (RSV), and attached it to a dendrimer by swapping it for a removable pyridinyldithio group. 'The preparation of the bioconjugates is very practical because of this exchange reaction and does not require additional reagents. It could be provided as a reaction kit, suitable to be used by any scientist,' says Harth. The disulfide bonds formed between the antibody and dendrimer are cleavable inside the cells and release the antibody in the biologically active state. 

The Nashville scientists tested their system on human epithelial cells infected with a genetically engineered version of RSV coupled to green fluorescent protein (GFP). GFP allowed the team to monitor the infected cells using imaging techniques such as confocal microscopy. The team noted that cells incubated with the dendrimer-antibody conjugate showed a reduction in viral production, with no evidence that the conjugate was toxic to the cells.  

"The reduction of 80-90 per cent in viral replication is a significant first step towards a new strategy for controlling disease"
- Craig Hawker

Craig Hawker, an expert on macromolecular assemblies and drug delivery, at the University of California, Santa Barbara, US, is enthusiastic about the research. 'This is extremely interesting and influential work,' he says. 'The reduction of 80-90 per cent in viral replication is a significant first step towards a new strategy for controlling disease,' adds Hawker. RSV remains the leading cause of bronchiolitis and pneumonia in infants and children. Although major advances have been made in bronchiolitis patient care, there is no effective treatment for the disease and the development of a safe and effective vaccine remains a major challenge.

Harth says that in the future, she hopes to extend the research to include not only other viruses such as HIV and rotoviruses, but also cancer and Huntingdon's disease.

Kathleen Too 

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Link to journal article

Effective delivery of IgG-antibodies into infected cells via dendritic molecular transporter conjugate IgGMT
Sharon K. Hamilton, Mine R. Ikizler, Christian Wallen, Peter F. Wright and Eva Harth, Mol. BioSyst., 2008, 4, 1209
DOI: 10.1039/b816645e

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