Figure 3

Different therapeutic approaches based on H19-IGF2 gene loci for the treatment options of lung tumorigenesis. Different therapeutic approaches can be harnessed to target specifically lung cancer cells with aberrant H19/miR-675 and IGF2/miR483 expressions. (Left): Transcriptional targeting approach utilizes transcription factors that activate the expression of the endogenous H19 lncRNA to drive the expression of a cytotoxic gene (DT-A) from the therapeutic plasmid vector (BC-819) in a manner specific for tumor expressing H19 gene products. BC-821 therapeutic vector in addition to H19-DT-A cassette contains another therapeutic cassette that drive the expression of DT-A under the transcriptional control of P4-IGf2 promoter. Thus BC-821 would increase both the cell killing capacity and the therapeutic index. (Right): Different cancer specific transcriptional products of the H19-IGF2 loci ( e.g. H19, miR-675, P4-IGF2, miR-483), can be specifically knocked down alone or in combinations utilizing siRNA and antisense technologies. The phenotype predicted is retardation of lung cancer growth and progression depending on the targeted product.