This invention relates to methods for manipulating the immune system using small interfering RNA (siRNA). Potential applications include the development of organ storage/reperfusion solutions and treatments for a broad range of disease indications.

This discovery identifies methods of manipulating immune system using small interfering RNA (siRNA). The inventors have demonstrated that manipulating a certain immune system cell called the dendritic cell with siRNA can lead to potent immune modulation in vitro and in vivo. This approach is thousands of times more potent than conventional gene blocking techniques, is pharmacokinetically appealing, and does not induce systemic toxicity at therapeutically effective concentrations. For example, suppression of the immune stimulatory gene interleukin-12 has been achieved with picomolar quantities of siRNA. Further, the power and stability of the technique of this invention has been revealed by data showing that administration of siRNA-manipulated dendritic cells into a recipient mouse will alter subsequent immune response. 

Manipulation of immunological responses offers therapeutic possibilities for a variety of diseases associated with immune hyperactivation (i.e. transplant rejection, multiple sclerosis, arthritis, and diabetes) or immune underactivation (i.e. HIV, viral infections, and cancers). Many approaches have previously been used for altering the immune response including antibodies, administration of cytokines, and antisense oligonucleotides. With few exceptions, these approaches have been difficult to translate clinically due to toxicity, poor pharmacokinetics, and inefficiency at tolerable doses. This technology offers a powerful new method for attacking immunological disorders which is applicable to a broad range of disease indications.

Market Opportunity:

Although the North American market for immunomodulatory agents is very large, specific indications that are presently under development include organ transplantation ($2.2 billion/year), organ storage solution ($200 million/year), and autoimmune diseases ($20 billion/year).