Fusions of elastin-like polypeptides to pharmaceutical proteins.
Elastin-like polypeptides (ELPs) are a class of stimulus-responsive biopolymers whose physicochemical properties and biocompatibility are particularly suitable for in vivo applications, such as drug delivery and tissue engineering. The lower critical solution temperature (LCST) behavior of ELPs allows them to be utilized as soluble macromolecules below their LCST, or as self-assembled nanoscale particles such as micelles, micron-scale coacervates, or viscous gels above their LCST, depending on the ELP architecture. As each ELP sequence is specified at its genetic level, functionalization of an ELP with peptides and proteins is simple to accomplish by the fusion of a gene encoding an ELP with that of the peptide or protein of interest. Protein ELP fusions, where the appended protein serves a therapeutic or targeting function, are suitable for applications in which the ELP can improve the systemic pharmacokinetics and biodistribution of the protein, or can be used as an injectable depot for sustained, local protein delivery. Here we describe considerations in the design of therapeutic protein ELP fusions and provide details of their gene design, expression, and purification.
Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA.
Wafa
W
Hassouneh
Sarah R
SR
MacEwan
Ashutosh
A
Chilkoti
D001483:Base Sequence; D002626:Chemistry, Pharmaceutical; D003001:Cloning, Molecular / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D004549:Elastin / Q000235:genetics* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli; D006801:Humans; D008823:Micelles; D008969:Molecular Sequence Data; D009391:Nephelometry and Turbidimetry; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D044367:Phase Transition; D010957:Plasmids / Q000737:chemistry / Q000235:genetics*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D013696:Temperature; D014169:Transformation, Bacterial
D008823:Micelles; D010455:Peptides; D011993:Recombinant Fusion Proteins; D004549:Elastin