Targeted delivery of plasmid DNA into the nucleus of cells via nuclear localization signal peptide conjugated to DNA intercalating bis- and trisacridines

TY - JOUR

T1 - Targeted delivery of plasmid DNA into the nucleus of cells via nuclear localization signal peptide conjugated to DNA intercalating bis- and trisacridines

AU - Shiraishi, Takehiko

AU - Hamzavi, Ramin

AU - Nielsen, Peter E.

PY - 2005/9/22

Y1 - 2005/9/22

N2 - Efficient nuclear targeting via nonviral delivery of DNA is still an unmet challenge in gene therapy. We have synthesized a novel 9-aminoacridine amino acid monomer that conveniently allows multiple acridines to be incorporated into peptide conjugates. In particular we have prepared bis- and trisacridine conjugates of nuclear localization signal peptide (NLS) ((Acr)2-NLS and (Acr)3-NLS) and studied these as functional transporters for the nuclear delivery of DNA. We show that these conjugates can enhance transfection efficacy as well as nuclear localization of plasmid DNA by more than 50-fold when combined with polyethylenimine at an N:P ratio of 2-3. These conjugates have high reversible affinity for double stranded DNA by intercalation and the technique provides a simple means of associating NLS with DNA of any sequence and at any ratio.

AB - Efficient nuclear targeting via nonviral delivery of DNA is still an unmet challenge in gene therapy. We have synthesized a novel 9-aminoacridine amino acid monomer that conveniently allows multiple acridines to be incorporated into peptide conjugates. In particular we have prepared bis- and trisacridine conjugates of nuclear localization signal peptide (NLS) ((Acr)2-NLS and (Acr)3-NLS) and studied these as functional transporters for the nuclear delivery of DNA. We show that these conjugates can enhance transfection efficacy as well as nuclear localization of plasmid DNA by more than 50-fold when combined with polyethylenimine at an N:P ratio of 2-3. These conjugates have high reversible affinity for double stranded DNA by intercalation and the technique provides a simple means of associating NLS with DNA of any sequence and at any ratio.

KW - Acridines/chemistry

KW - Biological Transport

KW - Cell Nucleus/metabolism

KW - DNA/chemistry

KW - Electrophoretic Mobility Shift Assay

KW - Nuclear Localization Signals/chemistry

KW - Plasmids/chemistry

KW - Transfection

U2 - 10.1021/bc050093f

DO - 10.1021/bc050093f

M3 - Journal article

C2 - 16173787

SN - 1043-1802

VL - 16

SP - 1112

EP - 1116

JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

IS - 5

ER -