Immunostimulation Screening

Once a small set ( 10) of potent candidate siRNAs have been identified, the molecules are screened for potential acute pro-inflammatory effects in an in vitro human whole blood cytokine assay and in vivo in the outbred CD-I mouse. 

DISCOVERY AND DEVELOPMENT STRATEGIES FOR SMALL INTERFERING RNAs 

The in vitro human whole blood assay and the outbred mouse are considered binary (yes/no) hazard identification tools in lead optimization screening for compound selection. In our experience to date, chemically modified conjugate siRNAs do not provoke acute pro-inflammatory effects in subsequent rodent or nonrodent studies or in clinical trials if they test negative in these two assays. Lacking positive controls, it is not yet feasible to assess whether the immuno-stimulation screening during lead optimization is predictive or relevant for human outcomes. 

---

In order to rationally apply immunostimulants of plant origin, however, it is necessary to search for the active principles of these substances and to produce them in a pure form. Because suitable screening methods have become available only recently, research in this field is in its very beginning. Further progress can be expected from systematic basic research on the mechanisms underlying immunomodulation. This also applies to verification of clinical efficacy, which is a prerequisite for the acceptance of medications with purported immunostimulatory properties. 

The results of more than 15 years of screening experience in the author s laboratory has shown that the best short cut to finding in vivo effective immunostimulants are investigations using experimental animals and infectious stress or immunosup-... 

Using random screening methods or taking hints from Ayurvedic uses (like in infections) several plants which are not rasayanas have also been identified as immunostimulants. 

---