| Autor: |
de Brito E Cunha D; Immunological Technology Laboratory, Institute of Technology in Immunobiologicals, Bio-Manguinhos, Oswaldo Cruz Foundation, Fiocruz, Rio de Janeiro 21040-900, Brazil., Frederico ABT; Immunological Technology Laboratory, Institute of Technology in Immunobiologicals, Bio-Manguinhos, Oswaldo Cruz Foundation, Fiocruz, Rio de Janeiro 21040-900, Brazil., Azamor T; Immunological Technology Laboratory, Institute of Technology in Immunobiologicals, Bio-Manguinhos, Oswaldo Cruz Foundation, Fiocruz, Rio de Janeiro 21040-900, Brazil., Melgaço JG; Immunological Technology Laboratory, Institute of Technology in Immunobiologicals, Bio-Manguinhos, Oswaldo Cruz Foundation, Fiocruz, Rio de Janeiro 21040-900, Brazil., da Costa Neves PC; Immunological Technology Laboratory, Institute of Technology in Immunobiologicals, Bio-Manguinhos, Oswaldo Cruz Foundation, Fiocruz, Rio de Janeiro 21040-900, Brazil., Bom APDA; Immunological Technology Laboratory, Institute of Technology in Immunobiologicals, Bio-Manguinhos, Oswaldo Cruz Foundation, Fiocruz, Rio de Janeiro 21040-900, Brazil., Tilli TM; Translational Oncology Platform, Center for Technological Development in Health, Oswaldo Cruz Foundation, Fiocruz, Rio de Janeiro 21040-900, Brazil.; Laboratory of Cardiovascular Research, Oswaldo Cruz Foundation, Fiocruz, Rio de Janeiro 21040-900, Brazil., Missailidis S; Immunological Technology Laboratory, Institute of Technology in Immunobiologicals, Bio-Manguinhos, Oswaldo Cruz Foundation, Fiocruz, Rio de Janeiro 21040-900, Brazil. |
| Abstrakt: |
The depth and versatility of siRNA technologies enable their use in disease targets that are undruggable by small molecules or that seek to achieve a refined turn-off of the genes for any therapeutic area. Major extracellular barriers are enzymatic degradation of siRNAs by serum endonucleases and RNAases, renal clearance of the siRNA delivery system, the impermeability of biological membranes for siRNA, activation of the immune system, plasma protein sequestration, and capillary endothelium crossing. To overcome the intrinsic difficulties of the use of siRNA molecules, therapeutic applications require nanometric delivery carriers aiming to protect double-strands and deliver molecules to target cells. This review discusses the history of siRNAs, siRNA design, and delivery strategies, with a focus on progress made regarding siRNA molecules in clinical trials and how siRNA has become a valuable asset for biopharmaceutical companies. |
