Human β-Globin Gene Cluster Transfer Mediated By Targeting Vectors Derived From Human Chromosomes

Safety and efficiency comprise the two important issues now faced by the community of gene therapy research and clinical trials. Although many factors, such as the choice of diseases, therapeutic genes, target cells, as well as the controllable expression of the repaired genes, affect these two big issues, gene delivery system is still the central part. Currently used gene delivery systems are classified into two groups, viral and non-viral vector systems. Viral vector system has the advantages of highly efficient transduction, stable integration and wide range of host cells, hence over 80% of the research projects adopted it. However, besides the general disadvantages of non-specificity, limited capacity and complicated packaging, the viral vector systems still has some severe safety problems - immunogenicity and insertional mutagenesis.In order to solve these problems, more researchers have turned to the safer, non-viral vector system, which has been largely ignored in the past. Non-viral vectors have important safety advantages over viral approaches, including their reduced pathogenicity and capacity for insertional mutagenesis, as well as their low cost and ease of production. The research of non-viral vectors now mainly focuses on targeting ability, transfection approaches and efficiency issues. One completely new application of non-viral vectors successfully utilizes the homologous recombination (HR) strategy to achieve specific genomic integration and long-term gene expression. According to this strategy, Xia's laboratory constructed a human chromosome derived, HR based vector BACMS, using the homologous sequence from the last intron of MLL3 located at human chromosome 7q36.2, and inserted the positive-negative selection markers, neo and HSVtk, inside and outside the homologous region respectively.Human globin gene family includes α and β gene clusters, among which the...