BACKGROUND: Human papillomavirus 16 (HPV16) is a high-risk DNA tumour virus, 
which is a major causative agent of cervical cancer. Cellular transformation is 
associated with deregulated expression of the E6 and E7 oncogenes. E7 has been 
shown to bind a number of cellular proteins, including the cell cycle control 
protein pRb. In this study, RNA aptamers (small, single-stranded 
oligonucleotides selected for high-affinity binding) to HPV16 E7 were employed 
as molecular tools to further investigate these protein-protein interactions.
METHODOLOGY/PRINCIPAL FINDINGS: This study is focused on one aptamer (termed 
A2). Transfection of this molecule into HPV16-transformed cells resulted in 
inhibition of cell proliferation (shown using real-time cell electronic sensing 
and MTT assays) due to the induction of apoptosis (as demonstrated by Annexin 
V/propidium iodide staining). GST-pull down and bead binding assays were used to 
demonstrate that the binding of A2 required N-terminal residues of E7 known to 
be involved in interaction with the cell cycle control protein, pRb. Using a 
similar approach, A2 was shown to disrupt the interaction between E7 and pRb in 
vitro. Furthermore, transfection of HPV16-transformed cells with A2 appeared to 
result in the loss of E7 and rise in pRb levels, as observed by immunoblotting.
CONCLUSIONS/SIGNIFICANCE: This paper includes the first characterisation of the 
effects of an E7 RNA aptamer in a cell line derived from a cervical carcinoma. 
Transfection of cells with A2 was correlated with the loss of E7 and the 
induction of apoptosis. Aptamers specific for a number of cellular and viral 
proteins have been documented previously; one aptamer (Macugen) is approved for 
clinical use and several others are in clinical trials. In addition to its role 
as a molecular tool, A2 could have further applications in the future.