title: Targeted disruption of β-arrestin 2-mediated signaling pathways by aptamer chimeras leads to inhibition of leukemic cell growth.
abstract: β-arrestins, ubiquitous cellular scaffolding proteins that act as signaling mediators of numerous critical cellular pathways, are attractive therapeutic targets because they promote tumorigenesis in several tumor models. However, targeting scaffolding proteins with traditional small molecule drugs has been challenging. Inhibition of β-arrestin 2 with a novel aptamer impedes multiple oncogenic signaling pathways simultaneously. Additionally, delivery of the β-arrestin 2-targeting aptamer into leukemia cells through coupling to a recently described cancer cell-specific delivery aptamer, inhibits multiple β-arrestin-mediated signaling pathways known to be required for chronic myelogenous leukemia (CML) disease progression, and impairs tumorigenic growth in CML patient samples. The ability to target scaffolding proteins such as β-arrestin 2 with RNA aptamers may prove beneficial as a therapeutic strategy.
  
  
  CONCLUSIONS
  An RNA aptamer inhibits β-arrestin 2 activity.Inhibiting β-arrestin 2 impedes multiple tumorigenic pathways simultaneously.The therapeutic aptamer is delivered to cancer cells using a cell-specific DNA aptamer.Targeting β-arrestin 2 inhibits tumor progression in CML models and patient samples.
authors.affiliation: Departments of Surgery and Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Kotula
authors.affiliation: Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Jinpeng
authors.initials: J
authors.lastname: Sun
authors.affiliation: Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Margie
authors.initials: M
authors.lastname: Li
authors.affiliation: Departments of Surgery and Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Pratico
authors.affiliation: Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Fereshteh
authors.affiliation: b3 bio, Inc. Research Triangle Park, North Carolina, United States of America.
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Ahrens
authors.affiliation: Departments of Surgery and Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Sullenger
authors.affiliation: Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina, United States of America; b3 bio, Inc. Research Triangle Park, North Carolina, United States of America.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Kovacs
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019390:Arrestins / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
chemical_list: C000605254:ARRB2 protein, human; D052157:Aptamers, Nucleotide; D019390:Arrestins; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
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