The major challenges to application of siRNA therapeutics include the stability and effective delivery of siRNA in vivo.
GPCRs that have received recent attention in the field of diabetes therapeutics include the incretin receptors (GLP1R, GIPR), GPR119, FFAR1 (GPR40), FFAR4 (GPR120) and the bile acid receptor GPBAR1 (TGR5) (for examples, see [ 2, 3, 5– 7]) (see text box).
While significant progress has been made in therapeutic antibodies, perhaps the most rapid advances have been made in nonantibody therapeutics, including the development of small-molecule inhibitors that modulate key pathways important in NHL pathogenesis.
Recent strategies to target VAR for small-molecule therapeutics included the use of polymerase inhibitors, notably Cidofovir, inhibitors of extracellular virus formation and tyrosine kinase inhibitors including Gleevec.
Of these genes, EPCAM stands out because opportunely, several monoclonal antibodies have already been developed against EPCAM as cancer therapeutics, including the well-tolerated, fully humanized version, adecatumumab [ 59].
Other major challenges for RNAi-based cancer therapeutics include controlling the specificity of the siRNA, minimizing off-target effects, increasing resistance to nuclease degradation, and avoiding immune responses such as α/ β interferons, RNA-dependent kinase effects, and toll-like immunity.
Gene-expression profiling provided further support that the system faithfully models human epithelial cancer, and inhibitor studies indicate that it could be used to screen for new therapeutics, including those that target the tumour microenvironment.
Current EGFR-targeting therapeutics include antibodies targeting the extracellular domains, and small molecules inhibiting the intracellular kinase domain.
The cell membrane is a critical barrier to effective delivery for many therapeutics, including those which are nanoparticle-based.
Advantages of RNAi-based therapeutics include relatively fast initial screening and the ability to target proteins not yet addressable by traditional drug design strategies.
The properties of haemoglobin therapeutics include effective transport and delivery of oxygen, much like red cells.
