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Flu (Influenza)

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Fighting Back: New Drugs Against Flu (2004)

The traditional advice for treating flu—bed rest and fluids—works quite well in most cases. For the elderly, the very young and people with chronic illness, however, flu and its complications can be life-threatening. While several drugs exist to treat flu, they must be taken within 48 hours of the start of the illness. NIAID grantee Jianzhu Chen, Ph.D., is exploring ways some futuristic technologies might lead to better flu drugs.

A Welcome Interference

RNA interference (RNAi) is a cellular phenomenon that scientists are just now starting to understand and exploit. Dr. Chen and his colleagues at the Massachusetts Institute of Technology are exploring the possibility of using RNAi to hinder the ability of the flu virus to multiply inside its target cells. RNAi can selectively inhibit gene activity in cells; essentially, the technique allows researchers to “turn off” individual genes. Dr. Chen and his team have experimented with a particular form of RNAi, called short interfering RNA (siRNA), specific for genes that the flu virus requires to reproduce inside human cells.

In laboratory-grown cells and chicken embryos, the siRNAs exhibited a powerful effect on the virus' ability to make new copies of itself. Moreover, the tested siRNAs worked even at extremely small amounts, opening the possibility that they might prevent the flu virus from gaining a foothold and turning into full-blown disease. Also, the researchers note, siRNAs are attractive as potential flu preventives or drugs because they could be given through the nose and upper respiratory tract where flu viruses first enter the body.

Dr. Chen notes several key benefits of using siRNAs to halt the influenza virus:

  • A cocktail of siRNAs targeting different influenza virus genes can prevent the emergence of resistant virus strains
  • In mice, siRNAs can be used to both prevent and treat influenza virus
  • Because siRNAs are designed to target regions of the influenza virus genome that are less likely to mutate, they can be used to prevent or treat influenza strains of both human and avian origin

The latter two points were demonstrated in two studies, one published by Dr. Chen and colleagues in 2004 in Proceedings of the National Academy of Sciences, "Inhibition of influenza virus production in virus-infected mice by RNA interference," in which siRNA prevented and treated influenza virus infection in mice, including the highly pathogenic avian influenza viruses H5N1 and H7N7.

Additional publications about the use of siRNAs to prevent and treat flu by Dr. Chen and his colleagues include reports in the journals Expert Opinion on Biological Therapy and Virus Research.

References:

Q Ge et al. RNA interference of influenza virus production by directly targeting mRNA for degradation and indirectly inhibiting all viral RNA transcription. Proc Natl Acad Sci 100(5):2718-23. DOI: 10.1073/pnas.0437841100 (2003).

Q Ge et al. Inhibition of influenza virus production in virus-infected mice by RNA interference. Proc Natl Acad Sci 101(23):8676-81. DOI: 10.1073/pnas.0402486101 (2004).

M Thomas et al. Polycation-mediated delivery of siRNAs for prophylaxis and treatment of influenza virus infection. Expert Opin Biol Ther 5(4):495-505. DOI: 10.1517/14712598.5.4.495 (2005).

Q Ge et al. Use of siRNAs to prevent and treat influenza virus infection. Virus Research 102(1):37-42. DOI: 10.1016/j.virusres.2004.01.013 (2004).


Last Updated March 12, 2013

Last Reviewed March 12, 2013