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Bo Wu

Bo Wu, PhD Bo Wu, PhD
Research Scientist, Oligonucleotide Therapeutics Group
McColl-Lockwood Laboratory for Muscular Dystrophy Research
Department of Neurology

Prior Positions and Experience

2005-2006 Post-doctoral Fellow, University of California (San Francisco)
2004-2005 Post-doctoral Fellow, Kansai Medical University (Osaka, Japan)
2001 Visiting Scholar, Kansai Medical University (Osaka, Japan)
1997-2001 Lecturer and Assistant Professor, China Medical University (Shenyang, China)

Education

PhD: 2004, Kansai Medical University (Osaka, Japan)
MS: 1997, Shenyang Pharmaceutical University (Shenyang, China)
BS: 1994, Shenyang Pharmaceutical University (Shenyang, China)

Non-Viral Based Oligonucleotide Therapy for Muscular Dystrophies

Dr. Wu’s current main research interests are to develop safe and effective oligonucleotide therapy and non viral-mediated gene delivery for the treatment of muscular dystrophy. Antisense oligonucleotide (AON) therapy has been recently demonstrated with great potential to develop into treatment of muscular dystrophy. The principle of this therapy is that sequence specific AONs can induce targeted exon skipping to correct the reading frame of mutated dystrophin mRNA. The potential of AON-mediated exon skipping for treating muscular dystrophy has been initially demonstrated in cell culture systems and in the dystrophic mdx mouse. However, systemic exon skipping and induction of dystrophin protein by current antisense chemistries have been limited to a proportion of dystrophic skeletal muscle fibers and are barely detectable in the cardiac muscle due to difficulties in effective delivery of oligonucleotides into targeted tissues in vivo. This could severely reduce the therapeutic value of AONs in muscular dystrophies.

The goals of Dr. Wu’s research are to establish a safe and effective delivery system and to design optimal oligonucleotide sequences for delivery. The laboratory explores different strategies to improve antisense systemic effect in the mdx mice in vivo by modifying AONs with cell-penetrating peptides or peptide-like polymers. Current study demonstrates that it is now possible to restore fully dystrophin expression in all body muscles including the cardiac and diaphragm muscles in dystrophic mdx mice, a disease model of Duchenne muscular dystrophy with improved muscle pathology and functions. Further study will determine the long term effects and toxicity of the AONs in vivo, to screen and select AONs sequences specific for skipping exons of human dystrophin gene using transgenic mouse model carrying human dystrophin gene. This will establish a model for designing future clinical trial of oligonucleotide therapy.

Selected Peer-reviewed Publications

Wang M, Wu B, Lu P, Cloer C, Tucker J, Lu QL. Polyethylenimine Modified Pluronics (PCMs) Improve Morpholino Oligomer Delivery in Cell Culture and Dystrophic mdx Mice. Mol Ther 2013, 21 1, 210–216. doi:10.1038/mt.2012.236

The first two authors contributed equally to this work.

Wu B, Lu P, Cloer C, Shaban M, Grewal S, Milazi S, Shah S, Moulton HM, Lu QL. Long-Term Rescue of Dystrophin Expression and Improvement in Muscle Pathology and Function in Dystrophic mdx Mice by Peptide-Conjugated Morpholino. Am J Pathol. 2012, 181(2):392-400. [PMID: 22683468]

Wang M, Tucker J, Lu P, Wu B, Lu QL. Tris[2-(acryloyloxy)ethyl]isocyanurate Cross-Linked Low-Molecular-Weight Polyethylenimine as Gene Delivery Carriers in Cell Culture and Dystrophic mdx Mice, Bioconjugat.e Chem. 2012, 23, 837−845. [PMID: 22443086]

Wang M, Lu P, Wu B, Tucker J, Cloer C, Lu QL. High efficiency and low toxicity of polyethyleneimine modified Pluronics (PEI–Pluronic) as gene delivery carriers in cell culture and dystrophic mdx Mice, J. Mater. Chem. 2012, 22, 6038-6046. DOI: 10.1039/C2JM15625C

Lu QL, Wu B. Systemic delivery of antisense oligomer in animal models and its implications for treating DMD.Methods Mol Biol. 2012;867:393-405. [PMID: 22454075]

Wu B, Benrashid E, Lu P, Cloer C, Zillmer A, Shaban M, Lu QL. Targeted skipping of human dystrophin exons in transgenic mouse model systemically for antisense drug development. PLoS One. 2011;6(5):e19906. [PMID: 21611204]

Wu B, Xiao B, Cloer C, Shaban M, Sali A, Lu P, Li J, Nagaraju K, Xiao X, Lu QL. One-year treatment of morpholino antisense oligomer improves skeletal and cardiac muscle functions in dystrophic mdx mice. Mol Ther. 2011;19(3):576-83. [PMID: 21179007]

Hu Y, Wu B, Zillmer A, Lu P, Benrashid E, Wang M, Doran T, Shaban M, Wu X, Lu QL. Guanine Analogues Enhance Antisense Oligonucleotide-induced Exon Skipping in Dystrophin Gene In Vitro and In Vivo. Mol Therapy 2010 Jan 19. [Epub ahead of print] [PMID: 20087314]

The first two authors contributed equally to this work.

Moulton HM, Wu B, Jearawiriyapaisarn N, Sazani P, Lu QL, Kole R.Peptide-morpholino conjugate: a promising therapeutic for Duchenne muscular dystrophy. Ann N Y Acad Sci. 2009 Sep;1175:55-60. [PMID: 19796077]

Wu B, Lu P, Benrashid E, Malik S, Ashar J, Doran TJ, Lu QL. Dose-dependent restoration of dystrophin expression in cardiac muscle of dystrophic mice by systemically delivered morpholino.Gene Therapy 2010 Jan;17(1):132-40. [PMID: 19759562]

Lu QL, Wu B. Systemic Treatment of Duchenne Muscular Dystrophy by Antisense Oligomer-Induced Exon Skipping 2010;Ed Dongsheng Duan:Chapter 6. 85-97.

Wu B, Li Y, Morcos PA, Doran TJ, Lu P, Lu QL. Octa-guanidine morpholino restores dystrophin expression in cardiac and skeletal muscles and ameliorates pathology in dystrophic mdx mice. Mol Therapy 2009 May;17(5):864-71. [PMID: 19277018]

Wu B, Moulton HM, Iversen PL, Jiang J, Li J, Li J, Spurney CF, Sali A, Guerron AD, Nagaraju K, Doran T, Lu P, Xiao X, Lu QL. Effective rescue of dystrophin improves cardiac function in dystrophin-deficient mice by a modified morpholino oligomer. Proc Natl Acad Sci USA 2008 Sep 30; 105(39): 14814-9. [PMID: 18806224]

Doran TJ, Lu PJ, Vanier GS, Collins MJ, Wu B, Lu QL. Microwave irradiation enhances gene and oligonucleotide delivery and induces effective exon skipping in myoblasts. Gene Ther. 2009 Jan; 16(1): 119-28 [PMID: 18784750]

Zhang NY, Kitagawa K, Wu B, Xiong ZM, Otani H, Inagaki C. Chloride-dependency of amyloid beta protein-induced enhancement of glutamate neurotoxicity in cultured rat hippocampal neurons. Neurosci Lett 2006; 399: 175-180. [PMID: 16497436]

Wu B, Kitagawa K, Liu B, Zhang NY, Xiong ZM, Inagaki C. Attenuation of amyloid beta (Abeta)-induced inhibition of phosphatidylinositol 4-kinase activity by Abeta fragments, Abeta20-29 and Abeta31-35. Neurosci Lett 2006; 396: 148-152. [PMID: 16356635]

Wu B, Kitagawa K, Zhang NY, Liu B, Inagaki C. Pathophysiological concentrations of amyloid beta proteins directly inhibit rat brain and recombinant human type II phosphatidylinositol 4-kinase activity. J Neurochem 2004; 91: 1164-1170. [PMID: 15569259]

Wu, B, Kitagawa K, Yagyu K, Zhang NY, Hattori N, Inagaki C. Phosphatidylinositol and PI-4-monophosphate recover amyloid beta protein-induced inhibition of CI- -ATPase activity. Life Sci. 2002 Dec 20;72(4-5):455-63. [PMID: 12467886]

Research Support

Ongoing Research Support

NIH, NIMAS, 1P50AR060836-01. (Project PI, QI Long Lu; Program PI Eric Hoffman) 09-09-2011/08-31-2016
Center for Research Translation of Systemic Exon-skipping in Muscular Dystrophy. The aim of this project is to screen and identify antisense oligonucleotides for drug development and preparing for clinic trials.
Role: Co investigator

NIH, NINDS, 1U01NS062709-01A1, (PI, Qi Long Lu) 9/30/2009-9/29/2014
Antisense therapy for DMD-Optimization and toxicology of AON for exon 45 skipping 2009-2013. The aim of the project is to identify effective antisense oligomers for targeted exon 45 skipping and further drug development for treating applicable DMD patients.
Role: Co investigator

Completed Research Support

Department of Defense (USAMRMC) W81XWH-09-1-0599. (PI, QI Long Lu) 9/15/2008-9/14/2012
Antisense therapy for Duchenne muscular dystrophyMorpholino antisense oligonucleotide and systemic delivery. The aim of the project is to identify effective reagents for enhanced delivery of morpholino oligos systemically with low toxicity.
Role: Co investigator

North Carolina Biotechnology Center, Grant #2011-BRF-1204 (PI, MingXing Wang) 7/1/2010-12/31/2012
Amphiphilic Polymer Modified PMO for Treating Duchenne Muscular Dystrophy by Exon-Skipping.
Role: Co investigator

Patents/Applications

Mingxing Wang, Qi Long Lu, Bo Wu, Peijuan Lu.  "Amphiphilic cationic polymers and methods of use thereof”
US provisional application no. 61/535,798 filed 9/16/2011; US non-provisional application no. 13/619,067 filed 9/14/2012; International application no. PCT/US2012/055521 filed 9/14/2012

Qi Long Lu, Bo Wu. “Pharmaceutical Compositions Comprising Antisense Oligonucleotides and Method of Using Same”  US non-provisional application no. 12/800,376 filed 5/13/2010; PCT/US2011/034993 filed 5/3/2011

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