Synthetic vectors for gene therapy

Abstract

Gene therapy refers to the concept and practice of applying genes to the treatment of disease, including recessive monogenic disorders, cancers and viral infections. Genes or nucleic acid molecules that regulate gene expression must be delivered into cells of the appropriate organ or tissues affected by the disease, tumour etc. Generally, this requires the use of viral or non-viral gene delivery systems. Viral vectors, particularly retrovirus and adenovirus, have been widely used as they demonstrate high efficiency of gene delivery. However, they also suffer from limitations; retroviruses can only transduce rapidly dividing cells and integrate at random sites in the host genome posing the risk of random insertional mutagenesis and potential oncogenesis. Adenovirus on the other hand can transduce non-dividing cells and does not integrate necessitating, therefore, repeated vector administration. However, adenoviral use in vivo induces a strong inflammatory immune response, which both limits the duration of gene expression and reduces the efficacy of repeated vector administration. Synthetic vectors, on the other hand, offer much greater safety and ease of use. In addition, unlike viruses, there are no theoretical limitations to the amount of DNA that can be packaged. For many applications in gene therapy, therefore, synthetic systems offer an acceptable alternative strategy for gene delivery. Their major limitation, however, concerns their low level of transfection efficiency, sensitivity to plasma and serum proteins in vivo, and general formulation instability. This review presents and discusses progress in these and other areas concerning the development of synthetic vector systems for gene therapy.

• gene therapy
• gene transfer
• ligand
• liposome
• non-viral
• peptide
• targeted
• vectors