The invention relates to design of short oligonucleotides and analogs thereof (such as, di-, and trinucleotide compounds) useful for various therapeutic applications. It is believed that the compounds of the invention can be used as antiviral agents, anticancer agents and so on. In certain embodiments, the compounds of the invention can modulate immune-stimulatory pathways and non-TLR pathways. The invention also relates to design modified oligonucleotides for therapeutic applications, by excluding nucleotide segments having off-target effects from the modified oligonucleotides. In another aspect, the invention provides pharmaceutical compositions including one or more compounds of the invention.It is believed that the compounds and compositions as described herein have therapeutic utility against a variety of diseases, including viral diseases, autoimmune diseases (such as, allergy, asthma, and inflammatory disorders) and cancer.