biostudies-literatureMing XNIGMS NIH HHS6567-76https://www.ebi.ac.uk/biostudies/studies/S-EPMC2965246biostudies-literatureUnknown38(19)Gastrin-releasing peptide receptor (GRPR), a member of the G protein-coupled receptor superfamily, has been utilized for receptor-mediated targeting of imaging and therapeutic agents; here we extend its use to oligonucleotide delivery. A splice-shifting antisense oligonucleotide was conjugated to a bombesin (BBN) peptide, and its intracellular delivery was tested in GRPR expressing PC3 cells stably transfected with a luciferase gene interrupted by an abnormally spliced intron. The BBN-conjugate produced significantly higher luciferase expression compared to unmodified oligonucleotide, and this increase was reversed by excess BBN peptide. Kinetic studies revealed a combination of saturable, receptor-mediated endocytosis and non-saturable pinocytosis for uptake of the conjugate. The K(m) valNucleic acids researchIntracellular delivery of an antisense oligonucleotide via endocytosis of a G protein-coupled receptor.PMC2965246P01GM059299Fisher MJuliano RLAlam MRChen XYan YMing XfalseIntracellular delivery of an antisense oligonucleotide via endocytosis of a G protein-coupled receptor.Gastrin-releasing peptide receptor (GRPR), a member of the G protein-coupled receptor superfamily, has been utilized for receptor-mediated targeting of imaging and therapeutic agents; here we extend its use to oligonucleotide delivery. A splice-shifting antisense oligonucleotide was conjugated to a bombesin (BBN) peptide, and its intracellular delivery was tested in GRPR expressing PC3 cells stably transfected with a luciferase gene interrupted by an abnormally spliced intron. The BBN-conjugate produced significantly higher luciferase expression compared to unmodified oligonucleotide, and this increase was reversed by excess BBN peptide. Kinetic studies revealed a combination of saturable, receptor-mediated endocytosis and non-saturable pinocytosis for uptake of the conjugate. The K(m) val2010-01-01T00:00:00Z2010 Oct2025-04-22T05:22:45.76Z2019-03-27T00:35:13ZS-EPMC29652462055113110.1093/nar/gkq534