Moreover, this strategy introduces no mutation in virus protein, leaving virus packaging efficiency unharmed and thus without attenuation of adenovirus ability to kill cancer cells. Such a view has been repeatedly verified in previous two explorations and present study. Hence, the viral regulation strategy based on tissuespecific microRNA is promising to generate conditionally replicative adenoviruses. Since let-7 is expressed at lower levels in HCC cells than normal liver cells and can affect either the stability or translation of the target mRNA, it is feasible to decrease the Ad‘s liver tropism via introducing let-7 target sites to regulate E1A expression. As shown above, both mRNA and DAPT protein of the E1A was tightly regulated according to cellular let-7. Consequently, the replication of the engineered virus was decreased more than 300-fold compared to the control virus in normal liver cells, whereas the proliferation rate between the engineered virus and the control virus was similar in HCC cells. Accordingly, the cytotoxicity of the engineered virus was distinctly declined in normal liver cells while alomst not impaired in HCC cells. These results indicated that introduction of let-7 target sites downstream of E1A could successfully decrease the hepatotoxicity of wild-type adenovirus without attenuation of its ability to kill HCC cells with lower level of let-7. Thus, the engineered adenovirus fine-tuned by let-7 presented here may serve as a potential anticancer agent or a therapeutic vehicle for harboring antitumor genes, broadly applied in the treatment against cancer with the downregulated cellular let-7, including HCC. Spinal muscular atrophy is an autosomal recessive motor neuron disease that affects approximately 1 in 8,000 newborns. It is a leading cause of infant and childhood morbidity. The genetics of SMA are complex, but all patients have homozygous mutations in exon 7 of the survival of motor neuron gene on chromosome 5q13. These mutations result in decreased expression of SMN protein, which functions chiefly as part of a complex that plays a crucial role in eukaryotic mRNA processing. SMN protein is also transported in the axon, where it appears to play an important role in neuromuscular junction formation and axonal growth. The relative contribution of these functions to the pathogenesis of SMA is still unclear and a matter of some debate. A feature that makes SMA unique among human genetic diseases is that a genomic duplication at the SMN locus has resulted in a nearly identical gene, SMN2 that lies centromeric to the SMN1 gene and differs from SMN1 mainly by a single C to T nucleotide substitution at the splice junction of exon 7. This mutation does not affect the amino acid sequence, but does alter mRNA splicing in favor of transcripts lacking exon 7.