FUTURE DIRECTIONS OF FUNCTIONAL RNA ORIGAMI

After successfully demonstrating that our functional RNA origami can act as an anticoagulant, our future directions include:

CELL FACTORY

RNA production can occur in vivo by use of a cell factory. This enables mass production of the RNA origami, allowing RNA-based anticoagulants to be used in commercial and clinical settings.

Figure 1   In vivo  production of RNA origami

Figure 1 In vivo production of RNA origami

BEYOND ANTICOGULANTS: HIV THERAPY

RNA aptamers have the potential to be used to treat other clinical disorders, for example targeting viruses such as HIV. Exploiting RNA aptamers tethered on RNA origami, it might be possible to bind the virus and prevent its attachment to helper T cells. RNA aptamer targeted constructs could potentially inactivate virus and prevent it from doing considerable harm to the body’s immune system.

In the regulation of HIV gene expression, RNA sequences (TAR and RRE) are involved in recruiting regulatory proteins (tat and rev) (1). In order to disrupt viral gene expression, it may be possible to design RNA origami tethered with high affinity RNA aptamers raised against these regulatory proteins. The RNA origami may compete for binding of viral RNA and proteins and inhibit viral processes and reduce HIV propagation.

Figure 2  (A) Viral expression and (B) RNA origami disruption of viral expression

Figure 2 (A) Viral expression and (B) RNA origami disruption of viral expression

SMART CELLS

Smart cells are able to detect external signal from invaders and produce specific output to combat invaders. Development of this idea may be possible by integration of synthetic biology and nucleic acid nanotechnology. The signal from an invader could interact with an engineered receptor on a cell surface. Then, the receptor signal could activate an inducible promoter for production of functional RNA origami in order to bind and inhibit the invader or send optical output to notify a user. Smart cells might be used for biosensing and/or therapeutic applications.

Figure 3  Smart cells detect signal from invader and produce RNA origami to bind the invader

Figure 3 Smart cells detect signal from invader and produce RNA origami to bind the invader

REFERENCES

1. White, R. R., Sullenger, B.A., and Rusconi, C.P., Developing aptamers into therapeutics, J Clin Invest. 2000, 106, 929-34.

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