Conclusion

Adenoviruses can be utilized as a vector for the delivery of genetic material into cells. They possess many valuable characteristics, making them good candidates as gene therapy vectors. However, a major obstacle for clinical applications of adenoviral gene therapy vectors is the biodistribution of the virus. When administrated system-ically, over 90% of the administrated adenovirus ends up in the liver where it can cause liver toxicity. Two different approaches are being pursued to deal with this problem, referred to as either transductional or transcrip-tional retargeting.

Transductional retargeting is focused on preventing the liver uptake. Either by modifying or shielding the fiber knob, thereby inhibiting binding to the CAR receptor, or by shielding the complete adenovirus by means of PEG-ylation. The next step is the addition of a homing device for retargeting to the tissue or cell type of interest.

Transcriptional retargeting does not prevent liver uptake, but gene expression will only occur in the target tissue or cell type. This can be accomplished by placing the transgene under the control of a tumor- or tissue-specific promoter. When genes essential for adenoviral replication are placed under control of such a promoter selective replication will occur, thereby enhancing the efficiency of infection.

By combining these two fields of expertise it is possible to construct an adenovirus that, on one hand, circumvents the liver because it is transductional retargeted and homes to the tissue of interest. On the other hand, this adenovirus will selectively express the transgene in the targeted tissue.[10] This means that specificity is increased and therefore it is possible to systemically administrate a higher dosage of the adenovirus, increasing the efficiency of adenoviral gene therapy. It is also feasible to transductionally retarget CRAds. In this case more infectious viral particles will reach the tumor environment, increasing the initial infectious dose and subsequent infection efficiency.

Although much progress is made in the transductional and transcriptional retargeting of adenoviral vectors, there are still hurdles to overcome. Success in the clinic using CRAds is not convincing. One problem might be that tumors not only consist of tumor cells but also of connective tissue impairing the spread of the adenovirus throughout the tumor tissue. However, the combination of adenoviral vectors and chemotherapy seems to result in synergistic antitumor effects. Compared to other nonviral and viral vectors, the adenovirus is among the most efficient vectors currently used and is relatively harmless. Progress is made very rapidly and the use of adenoviruses in the clinic is a promising method for the treatment of cancer.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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