Bicistronic Lentiviruses Containing a Viral 2A Cleavage Sequence Reliably Co-Express Two Proteins and Restore Vision to an Animal Model of LCA1
2011

Bicistronic Lentiviruses Restore Vision in a Model of Leber Congenital Amaurosis

Sample size: 7 publication 10 minutes Evidence: moderate

Author Information

Author(s): Verrier Jonathan D., Madorsky Irina, Coggin William E., Geesey Mero, Hochman Michael, Walling Elleanor, Daroszewski Daniel, Eccles Kristofer S., Ludlow Rachel, Semple-Rowland Susan L.

Primary Institution: Department of Neuroscience, University of Florida McKnight Brain Institute, Gainesville, Florida, United States of America

Hypothesis

Can bicistronic lentiviral vectors effectively deliver multiple therapeutic proteins to restore vision in an animal model of Leber congenital amaurosis?

Conclusion

The study demonstrates that lentiviral vectors with 2A-like peptides can successfully express multiple proteins and restore vision in a chicken model of LCA1.

Supporting Evidence

  • Bicistronic lentiviral vectors were shown to express two proteins consistently in vitro.
  • Treatment with the 2A lentivector encoding GC1 restored vision in GUCY1*B chickens.
  • OKN reflexes were observed in treated animals, indicating restored visual function.
  • Transduction efficiency varied, with some retinas showing up to 16% area infected.

Takeaway

Researchers created a special virus that can deliver two proteins at once to help restore vision in blind chickens, and it worked well!

Methodology

The study involved designing lentiviral vectors with bicistronic transgenes and testing their efficacy in vitro and in vivo in GUCY1*B chickens.

Limitations

The study did not achieve permanent vision restoration, and the efficiency of transduction varied among treated animals.

Participant Demographics

GUCY1*B chickens, a model for human LCA1.

Statistical Information

P-Value

0.0007

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0020553

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