ABSTRACT

At first glance many viruses appear excellent candidates for therapeutic gene delivery, but increasing familiarity has exposed several weak points of these viral vectors that severely limit their usefulness. For adenoviral vectors, the benefits of an ability to infect a wide range of cells efficiently is counterbalanced by their immunogenicity, induction of inflammatory responses and difficulties of modifying their tropisms to gain selectivity towards appropriate cell targets. Similarly retroviruses show promise for cancer gene therapy through their selectivity for dividing cells, but similar problems of inappropriate tropisms, ready inactivation by complement and the risk of possible insertional mutagenesis, coupled with great difficulty of production of therapeutic viral titres has proved hard to overcome. Currently, of the viral vectors, adenoassociated virus is probably the most promising candidate, but again inappropriate tropisms, coupled with severe limitations on the size of therapeutic gene carried, limits its usefulness.