1. Field of the Invention
A perennial goal in the pharmacological arts has been the development of methods and compositions to facilitate the specific delivery of therapeutic and other agents to the appropriate cells and tissues that would benefit from such treatment, and the avoidance of the general physiological effects of the inappropriate delivery of such agents to other cells or tissues of the body. Recently, the advent of recombinant DNA technology and genetic engineering has provided the pharmacological arts with a wide new spectrum of agents that are functional genes carried in recombinant expression constructs capable of mediating expression of these genes in host cells. These developments have carried the promise of "molecular medicine", specifically gene therapy, whereby a defective gene could be replaced by an exogenous copy of its cognate, functional gene, thereby alleviating a variety of genetic diseases.
However, the greatest drawback to the achievement of effective gene therapy has been the inability in the art to introduce recombinant expression constructs encoding functional eukaryotic genes into cells and tissues in vivo. While it has been recognized in the art as being desirable to increase the efficiency and specificity of administration of gene therapy agents to the cells of the relevant tissues, the goal of specific delivery has not bee achieved in the prior art.
Liposomes have been used to attempt cell targeting. Rahman et al., 1982, Life Sci. 31: 2061-71 found that liposomes which contained galactolipid as part of the lipid appeared to have a higher affinity for parenchymal cells than liposomes which lacked galactolipid. To date, however, efficient or specific delivery has not been predictably achieved using drug-encapsulated liposomes. There remains a need for the development of a cell- or tissue-targeting delivery system.
Thus there remains in the art a need for methods and reagents for achieving cell and tissue-specific targeting of gene therapy agents, particularly recombinant expression constructs encoding functional genes, in vivo.