Key issues in non-viral gene delivery

The future of non-viral gene therapy depends on a detailed understanding of the barriers to delivery of polynucleotides. These include physicomechanic al barriers, which Limit the design of delivery devices, physicochemical ba rriers that influence self-assembly of colloidal particulate formulations, and biological barriers that compromise delivery of the DNA to its target s ite. It is important that realistic delivery strategies are adopted for ear ly clinical trials in non-viral gene therapy. In the longer term, it should be possible to improve the efficiency of gene delivery by learning from th e attributes which viruses have evolved; attributes that enable translocati on of viral components across biological membranes. Assembly of stable, org anized virus-like particles will require a higher level of control than cur rent practice. Here, we summarize present knowledge of the biodistribution and cellular interactions of gene delivery systems and consider how improve ments in gene delivery will be accomplished in the future. (C) 2001 Elsevie r Science B.V. All rights reserved.