Molecular breeding of viruses for targeting and other clinical properties

Modification of the tissue tropism and specificity of viral gene therapy ve ctors remains a major technical hurdle, despite the development of a wide v ariety of technical strategies for engineering the viral proteins. In this review we compare the advantages of the different approaches in use for modifying viral tropism. A new approach, called DNA shuffling or molecular breeding (by analogy to c lassical breeding), involves the homologous recombination of related DNA se quences obtained from the natural diversity of viral strains. This approach has proven to be very useful in many non-viral systems as well as in one v iral system. DNA shuffling is unique in that it permutates natural mutation s, which nature has already selected for function, leading to libraries of unusually high quality from which a wide variety of modified properties can be obtained.