One aspect of the present invention relates to a synthetic non-viral vector composition for gene therapy. Another aspect of the invention relates to the use of the composition for in vitro, ex vivo and/or in vivo transfer of genetic material. The invention also encompasses a pharmaceutical composition (useful for delivery of nucleic acids to a cell), containing a non-cationic amphiphilic molecule or macro-molecule; or a cationic amphiphilic molecule or macromolecule that transforms from a cationic entity to an anionic, neutral, or zwitterionic entity upon a chemical, photochemical, or biological reaction. Another aspect of the invention relates to multicationic compounds that are composed of three or more amino acids. The present invention also relates to the use of the pharmaceutical composition for delivery of nucleic acids to a cell. Moreover, the invention encompasses the non-viral vector compositions tethered to a surface. The surface-tethered compositions are useful for the delivery of nucleic acids to cells in contact with the surface. An additional embodiment of the invention relates to a hydrogel comprising a composition of the invention, and methods of using same for the delivery of genetic material to a cell.