Scavenger receptors in the cellular uptake of nucleic acids
Scavenger receptors are cell surface receptors with multiple functions in physiological processes like maintenance of homeostasis, clearance of apoptotic cells and pathogens. The ability of class A scavenger receptors to bind nucleic acids makes them particularly attractive as potential targets to address the uptake of nucleic acid based therapeutics. Very recently scavenger receptors were reported to mediate the uptake oligonucleotides complexed with cell penetrating peptides (CPPs). The novel CPPs of PepFect family very efficiently present nucleic acids to scavenger receptors and transfect cells. Harnessing of scavenger receptors could open new possibilities for application of nucleic acid based drugs in conjunction with CPPs, which on one hand enhance their efficacy and on the other, provide specificity of targeting.
SCAVENGER RECEPTORS AND THEIR LIGANDS
Scavenger receptors (SRs) are transmembrane proteins that were functionally defined by Brown and Goldstein in 1979 by their ability to bind and internalize modified low density lipoproteins (LDL) such as oxidized LDL (OxLDL) or acetylated LDL (AcLDL), but not native LDL molecules (1). Early studies of SRs were mainly focused on their role in lipid metabolism and atherosclerosis. Since the first discovery, the family of SRs has been markedly expanded and they are grouped into 8 classes, from A to H (2). Despite the structural differences between eight classes, all members of SRs share a common feature to bind and internalize negatively charged macromolecules or particles. Unlike other cell surface receptors, SRs exhibit unusually broad ligand binding repertoire, but still not all anionic molecules are ligands for SRs. In addition to the ability to capture modified LDL molecules, scavenger receptors bind polyribonucleotides such as polyinosinic acid (polyI) and polyguanilic acid (polyG), but not polyadenilic acid (polyA) and polycytidilic acid (polyC). SRs also associate natural or modified polysaccharides like carrage ...