title: Calcium condensed LABL-TAT complexes effectively target gene delivery to ICAM-1 expressing cells.
abstract: Targeted gene delivery using nonviral vectors is a highly touted scheme to reduce the potential for toxic or immunological side effects by reducing dose. In previous reports, TAT polyplexes with DNA have shown relatively poor gene delivery. The transfection efficiency has been enhanced by condensing TAT/DNA complexes to a small particle size using calcium. To explore the targetability of these condensed TAT complexes, LABL peptide targeting intercellular cell-adhesion molecule-1 (ICAM-1) was conjugated to TAT peptide using a polyethylene glycol (PEG) spacer. PEGylation reduced the transfection efficiency of TAT, but TAT complexes targeting ICAM-1 expressing cells regained much of the lost transfection efficiency. Targeted block peptides properly formulated with calcium offer promise for gene delivery to ICAM-1 expressing cells at sites of injury or inflammation.
authors.affiliation: Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66047, USA.
authors.forename: Supang
authors.initials: S
authors.lastname: Khondee
authors.forename: Abdulgader
authors.initials: A
authors.lastname: Baoum
authors.forename: Teruna J
authors.initials: TJ
authors.lastname: Siahaan
authors.forename: Cory
authors.initials: C
authors.lastname: Berkland
mesh_terms: D002118:Calcium; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D010455:Peptides / Q000009:adverse effects / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000009:adverse effects / Q000737:chemistry*
chemical_list: D010455:Peptides; D054322:tat Gene Products, Human Immunodeficiency Virus; D018799:Intercellular Adhesion Molecule-1; D011092:Polyethylene Glycols; D004247:DNA; D002118:Calcium