Synthetic triplex peptide nucleic acid-based inhibitors for cancer therapy
AssigneesUniversity of Connecticut, Beth Israel Deaconess Medical Center, Inc.
InventorsRaman Bahal, Karishma Dhuri, Frank Slack
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Abstract
A novel peptide nucleic acid (PNA) oligomer capable of forming a PNA/RNA/PNA triplex when binding to its target RNA is described. An anti-micro RNA (miRNA) capable of binding miR-155 was designed based on the novel PNA oligomer and was shown to significantly decrease miR-155 expression in vitro in lymphoma cell lines. In vivo testing in xenograft mouse models resulted in reduced miR-155 expression followed by reduced tumor growth. Methods of making and using the novel PNA oligomer for targeting other coding and noncoding RNAs are described.
Claims22
A peptide nucleic acid (PNA) oligomer that forms a PNA/RNA/PNA triplex structure, wherein the PNA oligomer has the formula:
- 5′-first PNA segment-flexible linker-second PNA segment-3′
- wherein
- the first PNA segment is complementary to a homopurine stretch in the ribonucleic acid (RNA),
- the second PNA segment is complementary to a region of the RNA including the homopurine stretch,
- the first PNA segment and the second PNA segment form the PNA/RNA/PNA triplex structure with the RNA, and
- the RNA is a coding or noncoding RNA.
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