Sunday, 01 May, 2016

Nonviral Gene Transfer by Sequence-Defined Proton-Sponges with Combined Nucleic Acid Binding and Endosomal Buffering: Balancing Basicities

U. Lächelt, A. K. Levacic, D. Wendel and E. Wagner -
Molecular Therapy, (2016)

The delivery of nucleic acids represents a therapeutic approach for the precise adjustment of cellular dysregulations on the genetic level. However, safe and efficient usage of therapeutic nucleic acids remains a challenging task since several barriers have to be overcome within the delivery pathway. Despite a lower efficiency compared to viral vectors, nonviral transfer systems also offer several advantages such as high control over structural design and properties, flexibility regarding cargo type and capacity and scalable manufacturing technologies. Polymers with protonatable amines are widely used as synthetic delivery systems since these compounds can fulfill several prerequisites such as nucleic acid binding, cellular uptake and endosomal release, as a result of their basic characteristics. To facilitate the individual delivery steps efficiently, sequential protonation in different pH ranges has to be provided by the transfecting agents. Herein solid-phase supported synthesis was used to set up a library of structurally related oligomers containing different oligoamino acid building blocks¹ and basic α-amino acids such as histidine and pyridylalanine...

Article on journal´s webpage