Cyclodextrin-polyethylenimine conjugates for targeted in vitro gene delivery

Many human gene therapies will require cell‐specific targeting. Though recombinant viruses are much more efficient than nonviral vectors, the latter, especially polymers, have the advantage of being targetable via conjugation of cell‐specific ligands, including sugars, peptides, and antibodies, whic...

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Bibliographic Details
Published in:Biotechnology and bioengineering 2005-02, Vol.89 (4), p.416-423
Main Authors: Forrest, M. Laird, Gabrielson, Nathan, Pack, Daniel W.
Format: Article
Language:English
Subjects:
amines
Antibodies
beta -Cyclodextrin
beta-Cyclodextrins - chemistry
Biological and medical sciences
Biotechnology
Cell Line
cyclodextrin
DNA
Fundamental and applied biological sciences. Psychology
gene delivery
Gene expression
Gene therapy
Gene transfer
Gene Transfer Techniques
Health. Pharmaceutical industry
Humans
Hydrophobicity
Industrial applications and implications. Economical aspects
Insulin
Luciferases - analysis
Luciferases - genetics
polyethyleneimine
Polyethyleneimine - chemistry
polyethylenimine
Polymers
Q1
Sugar
Transfection - methods
Viruses
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Summary:Many human gene therapies will require cell‐specific targeting. Though recombinant viruses are much more efficient than nonviral vectors, the latter, especially polymers, have the advantage of being targetable via conjugation of cell‐specific ligands, including sugars, peptides, and antibodies, which can be covalently attached to the polymer using a variety of chemistries. Cyclodextrin, which forms inclusion complexes with small hydrophobic molecules, has been incorporated into a gene‐delivery polymer and may provide a facile and versatile attachment site for targeting ligands. Polyethylenimine (PEI) was derivatized with β‐cyclodextrin on ∼10% of the polymer's amines (termed CD‐PEI). Human insulin was also derivatized with a hydrophobic palmitate group (pal‐HI), which could anchor the protein to CD‐PEI/DNA polyplexes. CD‐PEI was essentially nontoxic to HEK293 cells at concentrations optimal for gene delivery and mediated nearly 4‐fold higher gene expression than unmodified PEI, which is relatively toxic to these cells. More importantly, addition of the pal‐HI to CD‐PEI enhanced gene expression by more than an order of magnitude compared to unmodified PEI, either with or without the pal‐HI. Because of the relative ease with which CD‐binding moieties may be attached to various types of ligands, CD‐PEI may be a generally useful material for testing novel cell‐specific targeting compounds. © 2004 Wiley Periodicals, Inc.
ISSN:0006-3592
1097-0290
DOI:10.1002/bit.20356