Biological and Chemical Hybrid Vectors

Abstract

It is generally accepted that current gene delivery vectors, either viral or non-viral, have a number of drawbacks as ideal tools for gene therapy. Viral vectors have intrinsic efficient machineries for delivering their genomes into target cells, but it is not feasible to maintain the delivered genes stably beyond the characteristics of the parent virus genome in the cells. By contrast, non-viral (or synthetic) vectors can accommodate various genetic materials more flexibly than viral vectors, but their delivery machineries are still primitive and much less efficient than those of viral vectors. In order to overcome these difficult problems, Cotton and Wagner (1999) proposed the development of a novel non-viral vector equipped with the function of a viral vector, but the ideal vector still remains conceptual. In 1998, I proposed the development of a more concrete gene delivery system, the “hybrid vector” (Nakanishi et al. 1998). Hybrid vector is an ambiguous term, sometimes referring to non-viral vectors containing some biological moieties and sometimes to viral vectors combined with various synthetic materials. In this chapter, however, the term is used to describe the vector system defined as follows: Firstly, the hybrid vectors have a virus-like structure and function both for preserving their genetic materials and for efficiently delivering them into the target cells. Secondly, the hybrid vectors contain either DNA produced in a microorganism defective in DNA recombination or RNA, which in itself lacks the recombination mechanism. These genetic materials may also have the function to stabilize themselves in the cells. The most critical point in my proposal is to direct impartial attention to these two different aspects of the vector system (the gene delivery machineries and the genetic platforms to be installed in these machineries). Both of these aspects are equally important and relate with each other, as two sides of a coin. Development of a novel genetic platform is essential for curing patients suffering from congenital metabolic diseases, which is a difficult final goal of gene therapy. In this chapter, basic informa-