Dendrimeric siRNA for Efficient Gene Silencing†
Dr. Cheol Am Hong
Department of Biological Sciences, Department of Materials Science and Engineering, KI for NanoCentury (KINC CNiT), Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Republic of Korea)
Search for more papers by this authorDr. Ahmed A. Eltoukhy
Department of Biological Engineering, The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA)
Search for more papers by this authorProf. Hyukjin Lee
Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul (Republic of Korea)
Search for more papers by this authorProf. Robert Langer
Department of Biological Engineering, The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA)
Search for more papers by this authorCorresponding Author
Prof. Daniel G. Anderson
Department of Biological Engineering, The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA)
Daniel G. Anderson, Department of Biological Engineering, The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA)
Yoon Sung Nam, Department of Biological Sciences, Department of Materials Science and Engineering, KI for NanoCentury (KINC CNiT), Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Republic of Korea)
Search for more papers by this authorCorresponding Author
Prof. Yoon Sung Nam
Department of Biological Sciences, Department of Materials Science and Engineering, KI for NanoCentury (KINC CNiT), Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Republic of Korea)
Daniel G. Anderson, Department of Biological Engineering, The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA)
Yoon Sung Nam, Department of Biological Sciences, Department of Materials Science and Engineering, KI for NanoCentury (KINC CNiT), Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Republic of Korea)
Search for more papers by this authorDr. Cheol Am Hong
Department of Biological Sciences, Department of Materials Science and Engineering, KI for NanoCentury (KINC CNiT), Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Republic of Korea)
Search for more papers by this authorDr. Ahmed A. Eltoukhy
Department of Biological Engineering, The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA)
Search for more papers by this authorProf. Hyukjin Lee
Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul (Republic of Korea)
Search for more papers by this authorProf. Robert Langer
Department of Biological Engineering, The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA)
Search for more papers by this authorCorresponding Author
Prof. Daniel G. Anderson
Department of Biological Engineering, The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA)
Daniel G. Anderson, Department of Biological Engineering, The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA)
Yoon Sung Nam, Department of Biological Sciences, Department of Materials Science and Engineering, KI for NanoCentury (KINC CNiT), Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Republic of Korea)
Search for more papers by this authorCorresponding Author
Prof. Yoon Sung Nam
Department of Biological Sciences, Department of Materials Science and Engineering, KI for NanoCentury (KINC CNiT), Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Republic of Korea)
Daniel G. Anderson, Department of Biological Engineering, The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA)
Yoon Sung Nam, Department of Biological Sciences, Department of Materials Science and Engineering, KI for NanoCentury (KINC CNiT), Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Republic of Korea)
Search for more papers by this authorThis research was supported by Nano⋅Material Technology Development Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012M3A7B4049802).
Graphical Abstract
Self-assembly of siRNA molecules provides precisely controlled generation of dendrimeric siRNA nanostructures. The second-generation dendrimers can be complexed with a low-molecular-weight cationic polymer (PBAE) to generate stable nanostructures (ca. 160 nm diameter) by electrostatic interactions. Condensation and gene silencing efficiencies increase with increased generations of siRNA dendrimers owing to high charge density and structural flexibility.
Abstract
Programmable molecular self-assembly of siRNA molecules provides precisely controlled generation of dendrimeric siRNA nanostructures. The second-generation dendrimers of siRNA can be effectively complexed with a low-molecular-weight, cationic polymer (poly(β-amino ester), PBAE) to generate stable nanostructures about 160 nm in diameter via strong electrostatic interactions. Condensation and gene silencing efficiencies increase with the increased generation of siRNA dendrimers due to a high charge density and structural flexibility.
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