One of the most formidable impediments to clinical translation of RNA interference (RNAi) is safe and effective delivery of the siRNAs to the desired target tissue at therapeutic doses. We previously described in vivo cell type-specific delivery of anti-HIV small-interfering RNAs (siRNAs) through covalent conjugation to an anti-gp120 aptamer. In order to improve the utility of aptamers as siRNA...

Recently, we used in vitro selection to identify a new class of naturally occurring GTP aptamer called the G motif. Here we report the discovery and characterization of a second class of naturally occurring GTP aptamer, the "CA motif." The primary sequence of this aptamer is unusual in that it consists entirely of tandem repeats of CA-rich motifs as short as three nucleotides. Several active va...

In a recent issue of Science, Greenleaf et al. (2008) report single-molecule force measurements to explore the sequential folding landscape of an adenine riboswitch aptamer domain. This study provides an exceptionally quantitative view of how an RNA molecule folds.

RNA aptamers are oligonucleotides that bind with high specificity and affinity to target ligands. In the absence of bound ligand, secondary structures of RNA aptamers are generally stable, but single-stranded and loop regions, including ligand binding sites, lack defined structures and exist as ensembles of conformations. For example, the well-characterized theophylline-binding aptamer forms a ...

Purine riboswitches are RNA regulatory elements that control purine metabolism in response to intracellular concentrations of the purine ligands. Conformational changes of the guanine riboswitch aptamer domain induced by guanine binding lead to transcriptional regulation of genes involved in guanine biosynthesis. The guanine riboswitch aptamer domain has three RNA helices designated P1, P2, and...

RNA molecules are important cellular components involved in many fundamental biological processes. Understanding the mechanisms behind their functions requires RNA tertiary structure knowledge. Although modeling approaches for the study of RNA structures and dynamics lag behind efforts in protein folding, much progress has been achieved in the past two years. Here, we review recent advances in ...

Natural noncoding small RNAs have been shown to be involved in a number of cellular processes as regulators. Using the mechanisms thus elucidated, artificial small interfering RNAs (siRNAs), ribozymes, and RNA aptamers are also expected to be potential candidates for RNA therapeutic agents. However, current techniques are too costly for industrial production of these RNAs for use as drugs. Here...

RNA molecules uniquely form a complex through specific hairpin loops, called a kissing complex. The kissing complex is widely investigated and used for the construction of RNA nanostructures. Molecular switches have also been created by combining a kissing loop and a ligand-binding aptamer to control the interactions of RNA molecules. In this study, we incorporated two kinds of RNA molecules in...

The trans-activation (Tat) protein of human immunodeficiency virus type-1 (HIV-1) is vital for the replication of the virus. In a transcription assay i n v i t r o in the presence of authent ic TAR RNA, we found that authentic TAR RNA inhibits transcription from a template based on the CMV early promoter in a manner that is not related to the Tat/TAR interaction. Using variants of TAR RNA, we i...

In an effort to target the in vivo context of tumor-specific moieties, we screened a large library of nuclease-resistant RNA oligonucleotides in tumor-bearing mice to identify candidate molecules with the ability to localize to hepatic colon cancer metastases. One of the selected molecules is an RNA aptamer that binds to p68, an RNA helicase that has been shown to be upregulated in colorectal c...