Therapeutic applications of nucleic acids as ligands for Toll-like receptors

Gabriela Panter, Alenka Kuznik, Roman Jerala
Current Opinion in Molecular Therapeutics 2009, 11 (2): 133-45
Intracellular TLRs, represented by TLRs 3, 7, 8 and 9, are specialized for the recognition of different types of microbe-derived nucleic acids. However, endogenous nucleic acids can also activate these TLRs, triggering autoimmunity. Nucleic acid-sensing TLRs initiate innate immune responses upon infection, but these receptors also initiate the development of protective adaptive immune responses. Therefore, TLR stimulation represents an attractive strategy for the development of therapeutic and prophylactic agents targeting microbial infections, cancers and allergies. The current use of stimulatory nucleic acids targeting TLRs is reviewed for applications ranging from vaccine adjuvants to anticancer, antiviral and anti-allergic agents. In addition, inhibitory nucleic acid ligands being evaluated for their ability to ameliorate autoimmune disorders and viremias, such as systemic lupus erythematosus and HIV infection, respectively, are described.

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