Ligand targeting and peptide functionalized polymers as non-viral carriers for gene therapy

Polymeric gene carriers have been developed to deliver therapeutic genes for treating various genetic diseases. They may diminish the problems related with viral vectors in terms of safety, immunogenicity and mutagenesis. But inefficient endosomal release, cytoplasmic transport and nuclear entry are the main limiting issues in the usage of polymeric carriers. Different strategies have been proposed to functionalize gene carriers for individually overcoming these barriers. Towards this aim, various polymeric carriers have been developed and further modified with certain ligands and peptides to achieve properties like good cargo DNA protection, excellent colloidal stability, high cellular uptake efficiency, efficient endo/lysosome escape, efficient import into the nucleus and specificity to target cells. These multifunctional polymeric carriers are beneficial for efficient gene delivery. In this review, we provide a comprehensive summary of the interaction between gene and polymeric carriers and the mechanism and challenges of gene carriers. We also highlight and discuss the recent developments and advancements in the synthesis of ligand targeting and peptide functionalized gene carriers.