ω-Hydrazino Linear Polyethylenimine: A Monoconjugation Building Block for Nucleic Acid Delivery
✍ Scribed by Bénédicte Pons; Lila Mouhoubi; Abdennaji Adib; Przemyslaw Godzina; Jean-Paul Behr; Guy Zuber
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 330 KB
- Volume
- 7
- Category
- Article
- ISSN
- 1439-4227
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✦ Synopsis
Abstract
Nonviral gene therapy requires efficient vectors that are able to deliver nucleic acids inside the targeted cell nucleus. Developing new tools for the synthesis of supramolecular vectors with improved transfection efficiency and better biodistribution is therefore a crucial issue. Here we describe the synthesis of a 140‐mer linear polyethylenimine (L‐PEI) terminated at one end by a highly nucleophilic hydrazine residue. This cationic polymer, whose backbone is well known for its remarkable gene‐delivery efficiency, constitutes a building block for ω‐regioselective conjugation to molecules through the formation of stable linkages such as the hydrazone bonds. To demonstrate the potential of the ω‐hydrazino linear polyethylenimine, human serum transferrin, a ligand that is well know to improve gene‐delivery systems, was used as a model of sensitive material. The blood protein was oxidized to generate an aldehyde function and was subsequently conjugated to hydrazino PEI. The new polyethylenimine–transferrin (PEI–Tf) vector was purified and was shown to condense plasmid DNA into compact superstructures compatible with cellular uptake. Finally, the cellular‐binding and gene‐delivery properties of PEI/DNA polyplexes incorporating different quantities of transferrin were evaluated by FACS analysis and luciferase assay.