Commandeering a biological pathway using aptamer-derived molecular adaptors.
Induction of molecular proximity can mediate a discrete functional response in biological systems. Therefore, creating new and specific connectivity between non-interacting proteins is a means of imposing rational control over biological processes. According to this principle, here we use composite RNA aptamers to generate molecular adaptors that link various 'target' molecules to a common 'utility' molecule, with the utility molecule being an entry point to a pathway conscripted to process the target molecule. In particular, we created a bi-functional aptamer that simultaneously binds to the green fluorescent protein (serving as a surrogate extracellular target) and the opsonin C3b/iC3b (serving as the utility molecule). This bi-functional aptamer enabled us to commandeer the C3-based opsonization-phagocytosis pathway to selectively transport an extracellular target into the lysosome for degradation. This novel strategy has the potential for powerful therapeutic applications with extracellular proteins involved in tumor development or surface markers on cancer cells as the target molecules.
Mallik
Prabhat K
PK
Department of Biological Sciences and Institute for RNA Science and Technology, University at Albany, State University of New York, Albany, NY 12222, USA.
Nishikawa
Kimi
K
Millis
Albert J T
AJ
Shi
Hua
H
D052157:Aptamers, Nucleotide / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D003176:Complement C3 / Q000378:metabolism; D003179:Complement C3b / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008969:Molecular Sequence Data; D009895:Opsonin Proteins / Q000378:metabolism*; D021381:Protein Transport
D052157:Aptamers, Nucleotide; D003176:Complement C3; D009895:Opsonin Proteins; D049452:Green Fluorescent Proteins; D003179:Complement C3b