ABSTRACT

Our remedies oft in ourselves do lie, which we ascribe to heaven. The fated sky gives us free scope; only doth backward pull our slow designs when we ourselves are dull.

William Shakespeare, All’s Well That Ends Well

MicroRNA (miRNA) is a small and single-stranded RNA. miRNA inhibits expression of the target protein. miRNA precursor from the stem-loop structure is diced and can be considered a double-stranded RNA (dsRNA), which seems to closely resemble some short interfering RNAs (siRNAs). miRNA dominantly blocks protein translation based on its complementarity to the 3′ untranslated region (UTR) of mRNA, whereas in some cases, miRNA triggers the digestion of the mRNA transcript through RNA silencing machinery similar to siRNAs. Therefore, viral miRNAs can control gene expression of RNA viruses without causing the viral genomic RNA to be degraded by the latent infection. Although from in vivo prophylactic and therapeutic experiments with adult animals and from a phase I trial in humans, a small amount of trigger dsRNAs is sufficient to inactivate target viral RNAs without toxicity; the signal for miRNAs might imply spreading out to untreated cells and tissues as RNA waves, and then the information may be inherited by subsequent generations. To interfere with the viral replication cycle by suppression of expression of the latent viral genome, miRNA can be a workhorse

Overview ................................................................................................................ 333 18.1 Introduction .................................................................................................. 334 18.2 The RNA Waves Hypothesis ........................................................................ 334 18.3 Usage of Functional miRNAs for HIV-1 Therapy........................................ 337

18.3.1 Application of miRNAs for Oral/Edible Vaccine ............................ 337 18.3.2 An Overview of Usage of STYLE .................................................... 341

18.4 Rosetta Stone: An HIV-1 miRNAs Code ..................................................... 343 18.5 Conclusions ...................................................................................................344 Acknowledgments .................................................................................................. 345 References .............................................................................................................. 345

for development of nucleic acid drugs (NAD) and probably for an oral vaccine for HIV-1 infection.