Toshifumi Yokota

portrait of Toshi Yokota


8-29A Medical Sciences Building
Office: 780.492.1102
Yokota Lab Website


Dr. Yokota’s research goal is to discover, optimize, and translate novel therapies for neurological and musculoskeletal disorders. In particular, his research aims to develop and apply new methods, including genome editing and synthetic DNA-like molecules called antisense oligonucleotides. These new methods are applied to the correction of genetic mutations, drug discovery, new disease models, and answering fundamental biological questions. His studies led to the development of viltolarsen, an antisense oligonucleotide drug to treat Duchenne muscular dystrophy, which was approved in Japan in 2020 and is currently under review for FDA approval. He edited 2 protocol books on antisense-mediated exon skipping/inclusion and RNase H-inducing oligonucleotides called gapmers (Exon Skipping and Inclusion Therapies. Methods. Mol. Biol., 2018; Gapmers. Methods. Mol. Biol., 2020. Springer-Nature).

We currently focus on following projects:

1. Antisense and Genome Editing Therapies
Antisense-mediated therapy is an exciting new approach to treating diseases using DNA-like molecules. These molecules, called antisense oligonucleotides, act like a stitch or Band-Aid to mitigate the effects of genetic mutations and restore the gene function. By utilizing integrative experimental and computational approaches, such as antisense oligonucleotides, CRISPR/Cas9 genome editing, and machine-learning, the focuses of our group are to develop novel personalized molecular therapies for neuromuscular and musculoskeletal diseases. Our focus is on several devastating genetic diseases, including Duchenne/Becker muscular dystrophy (DMD/BMD), dysferlin-deficient muscular dystrophy (limb-girdle muscular dystrophy type 2b, Miyoshi myopathy, and distal myopathy with anterior tibial onset), facioscapulohumeral muscular dystrophy (FSHD), spinal muscular atrophy (SMA), giant axonal neuropathy (GAN), and fibrodysplasia ossificans progressiva (FOP).

2. Dystrophin Revertant Fibre Analysis
Duchenne muscular dystrophy (DMD) is one of the most common lethal genetic disorders, occurring once per 3,500 male births, caused by a lack of a protein called dystrophin. Interestingly, in many DMD patients and animal models, a small proportion of muscle fibres show strong dystrophin positive staining called "revertant fibres". We previously identified the mechanism by which revertant fibres arise from spontaneous exon skipping (alternative splicing) and proliferate through muscle regeneration with activation of muscle precursor (stem) cells. The aim of the current project is to elucidate the mechanisms underlying generation and proliferation of revertant fibres. By analyzing these fibres, researchers may be able to identify new and more effective targets for treatments of DMD.

3. Muscle Membrane Imaging
Some forms of muscular dystrophy patients including limb-girdle muscular dystrophy type 2B (LGMD2B), Miyoshi myopathy (MM), and distal myopathy with anterior tibial onset (DMAT) have a primary defect in skeletal muscle membrane repair. Their muscle fibres are unable to effectively repair the damaged muscle membrane. We analyze the molecular mechanisms involved in muscle membrane repair machinery with our state-of-the-art imaging infrastructure including multi-photon (two-photon) laser microscope. A better understanding of this process could lead to better treatments for patients. We are also developing antisense drugs to treat them.

4. Role of Water Channel Aquaporins in Muscle and Brain
A water channel Aquaporin-4 (AQP4) is known to selectively express in the fast-twitch skeletal muscle fibres and at the perivascular blood-brain-barrier (BBB) in the brain; however its physiological function remains poorly understood. In the past ten years, we have published several key findings related to the role of AQP4 in muscle fatigue and recovery using mutant mouse models. These include regulation of water flow across muscle membrane (sarcolemma) by AQP4 against osmotic changes and the recovery of muscle force generation after osmotic changes or exercise. The goal of our research program is to characterize the role of AQP4 in response to muscle exercise and fatigue in muscles and brains.

Selected Publications:


a) Journal Articles (Peer-reviewed)

66. Nguyen Q, Lim KRQ, Yokota T. (2020) Genome editing for the understanding and treatment of inherited cardiomyopathies. Int. J. Mol. Sci. 21:733

65. Lim KRQ, Nguyen Q, Yokota T. (2020) DUX4 signalling in the pathogenesis of facioscapulohumeral muscular dystrophy. Int. J. Mol. Sci. 21:729

64. Sato M, Shiba N, Miyazaki D, Shiba Y, Echigoya Y, Yokota T, Takizawa H, Aoki Y Takeda S, Nakamura A (2019) Amelioration of intracellular Ca2+ regulation by exon-45 skipping in Duchenne muscular dystrophy-induced pluripotent stem cell-derived cardiomyocytes. Biochem Biophys Res Commun. 520 (1), 179-185.

63. Roshmi R, Yokota T. (2019) Viltolarsen (NS-65/NCNP-01) for the treatment of Duchenne muscular dystrophy. Drugs of Today. 55 (10), 627-639.

62. Echigoya Y, Lim K, Nagata T, Kuraoka M, Kobayashi M, Aoki Y, Partridge T, Maruyama R, Takeda S, Yokota T. (2019) Exons 45-55 skipping using mutation-tailored cocktails of antisense morpholinos in the DMD gene. Mol. Ther. 27(11): 2005-17.
*For the first time, we demonstrated rescue of dystrophin expression using a cocktail of antisense oligonucleotides which is applicable to 47% of Duchenne muscular dystrophy patients.

61. Hwang J, Yokota T. (2019) Recent advancements in exon skipping therapies using antisense oligonucleotides and genome editing for the treatment of various muscular dystrophies. Expert Rev Mol Med. 21:e5

60. Nguyen Q, Lim K, Yokota T. (2019) Current Understanding and Treatment of Cardiac and Skeletal Muscle Pathology in Laminin-α2 Chain-Deficient Congenital Muscular Dystrophy. Appl Clin Genet. 12:113-130.

59. Nguyen Q, Yokota T. (2019) Antisense Oligonucleotides for the Treatment of Cardiomyopathy in Duchenne Muscular Dystrophy. Am J Transl Res.11(3):1202-1218 .

58. Lim K, Echigoya Y, Nagata T, Kuraoka M, Kobayashi M, Aoki Y, Partridge T, Maruyama R, Takeda S, Yokota T.(2019) Efficacy of multi-exon skipping treatment in Duchenne muscular dystrophy dog model neonates. Mol. Ther. 27(1): 76-86.

57. Miyatake S, Mizobe Y, Tsoumpra M, Lim KRQ, Hara Y, Shabanpoor F, Yokota T,Takeda S, Aoki Y. (2019) Scavenger receptor class A1 mediates uptake of morpholino antisense oligonucleotide into dystrophic skeletal muscle. Mol. Ther. Nucleic Acids. 14:520-535.

56. Shimizu-Motohashi Y, Komaki H, Motohashi N, Takeda S, Yokota T, Aoki Y. (2019) Restoring dystrophin expression in Duchenne muscular dystrophy: Current status of therapeutic approaches. J Pers Med. 9(1):1 .

55. Echigoya Y, Lim K, Nakamura A, Yokota T. (2018) Multiple exon skipping in the DMD hot spots: Prospects and challenges. J Pers Med. 8(4):41 .

54. Lim KRQ, Yoon C, Yokota T. (2018) Applications of CRISPR/Cas9 Exon Skipping for Duchenne Muscular Dystrophy. J Pers Med. 8(4):38.

53. Gordish-Dressman H, Willmann R, Dalle Pazze L, Kreibich A, van Putten M, Heydemann A, Bogdanik L, Lutz L, Davies K, Demonbruen AR, Duan D, Elsey D, Fukada S, Girgenrath M, Patrick Gonzalez J, Grounds MD, Nichols A, Partridge T, Passini M, Sanarica F, Schnell FJ, Wells DJ, Yokota T, Young CS, Zhong Z, Spurney C, Spencer M, De Luca A, Nagaraju K, Aartsma-Rus A. (2018) A Project to Improve How We Advance Duchenne Muscular Dystrophy Therapies to the Clinic- First Workshop Report: Examining current findings and opportunities around the emerging D2.B10-Dmd mdx /J (D2/mdx) model in context of the classic C57BL/10ScSn-Dmd mdx /J (Bl10/mdx). J Neuromuscul Dis. 5:407-417.

52. Lee JJA, Maruyama R, Duddy W, Sakurai H, Yokota T. (2018) Identification of novel antisense-mediated exon skipping targets in DYSF for therapeutic treatment of dysferlinopathy. Mol. Ther. Nucleic Acids. 13:596-604.

51. Lee JJA, Echigoya Y, Saito T, Duddy W, Aoki Y, Takeda S, Yokota T. (2018) Antisense PMO cocktails effectively skip dystrophin exons 45-55 in myotubes transdifferentiated from DMD patient fibroblasts. PLoS ONE. 13(5):e0197084.

50. Maruyama R, Touznik A, Yokota T. Evaluation of exon inclusion induced by splice switching antisense oligonucleotides in SMA patient fibroblasts. (2018) J Vis. Exp. 135.e57530.

49. Shimo T, Hosoki K, Nakatsuji Y, Yokota T, Obika S. (2018) A Novel Human Muscle Cell Model of Duchenne Muscular Dystrophy Created by CRISPR/Cas9 and Evaluation of Antisense-Mediated Exon Skipping. J. Hum. Genet. 63:89-92.

48. Lee JJA, Maruyama R, Sakurai H, Yokota T. (2018) Cell membrane repair assay using a two-photon laser microscope. J Vis. Exp.131, e56999

47. Aslesh T, Maruyama R, Yokota T. (2018)Skipping multiple exons to treat DMD - promises and challenges. Biomedicines. 2018, 6(1), 1

46. Echigoya Y, Nakamura A, Aoki Y, Nagata T, Kuraoka M, Urasawa N, Panesar D, Iversen P, Kole R, Maruyama R, Partridge T, Takeda S, Yokota T. (2017) Effects of systemic multi-exon skipping with peptide-conjugated morpholinos in the heart of a dog model of Duchenne muscular dystrophy. Proc. Natl. Acad. Sci. U S A.,114 (16), 4213-4218.

45. Echigoya Y, Lim K, Trieu N, Bao B, Miskew B, Vila MC, Novak JS, Hara Y, Lee J, Touznik A, Mamchaoui K, Aoki Y, Takeda S, Nagaraju K, Mouly V, Maruyama R, Duddy W, Yokota T. (2017) Quantitative antisense screening and optimization for exon 51 skipping in Duchenne muscular dystrophy. Mol Ther. 25(11): 2561-2572.

44. Lim K, Maruyama R, Yokota T. (2017) Eteplirsen in the treatment of Duchenne muscular dystrophy. Drug Design, Development and Therapy. 11: 533-545. *Top 0.1% citation according to Scopus

43. Nakamura A, Shiba N, Miyazaki D, Nishizawa H, Inaba Y, Fueki N, Maruyama R, Echigoya Y, Yokota T. (2017) Comparison of the phenotypes of patients harboring in-frame deletions starting at exon 45 in the Duchenne muscular dystrophy gene indicates potential for the development of exon skipping therapy. J. Hum. Genet. 62, 459-463.

42. Nguyen Q, Yokota T. (2017) Immortalized muscle cell model to test the exon skipping efficacy for Duchenne muscular dystrophy. J Pers Med. 7(4):13.

41. Touznik A, Maruyama R, Echigoya Y, Yokota T. (2017) LNA/DNA mixmer-based antisense oligonucleotides correct alternative splicing of the SMN2 gene and restore SMN protein expression in type 1 SMA fibroblasts. Sci Rep.7(1):3672.

40. Bao B, Maruyama R, Yokota T. (2016) Targeting RNA for the treatment of facioscapulohumeral muscular dystrophy. Intractable Rare Dis Res. 5(3):168-76.

39. Nichols B, Aoki Y, Kuraoka M, Lee JJA, Takeda S, Yokota T. (2016) Multi-exon Skipping Using Cocktail Antisense Oligonucleotides in the Canine X-linked Muscular Dystrophy. J Vis. Exp. 111: e53776

38. Nakamura A, Fueki N, Shiba N, Motoki H, Miyazaki D, Nishizawa H, Echigoya Y, Yokota T, Aoki Y, Takeda S. (2016) Deletion of exons 3-9 encompassing a mutational hot spot in the DMD gene presents an asymptomatic phenotype, indicating a target region for multiexon skipping therapy. J Hum Genet. 61(7):663-7.

37. Rodrigues M, Echigoya Y, Fukada S, Yokota T. (2016) Current Translational Research and Murine Models for Duchenne Muscular Dystrophy. J Neuromuscul Dis. 3(1): 29-48.

36. Kamaludin A, Smolarchuk C, Bischof JM, Eggert R, Greer JJ, Ren J Lee JJA, Yokota T, Berry FB, Wevrick R. (2016) Muscle dysfunction caused by loss of Magel2 in a mouse model of Prader-Willi and Schaaf-Yang syndromes. Hum. Mol. Genet. 25(17):3798-3809.

35. Rodrigues M, Echigoya Y, Maruyama R, Lim K, Fukada S, Yokota T. (2016) Impaired regenerative capacity and lower revertant fibre expansion in dystrophin deficient mdx muscles on DBA/2 background. Sci Rep. 6:38371.

34. Guncay A, Yokota T. (2015) Antisense oligonucleotide drugs for Duchenne muscular dystrophy: how far have we come and what does the future hold? Future Med Chem. 7(13):1631-5.

33. Pandey SN, Kesari A, Yokota T, Pandey GS. (2015) Muscular Dystrophy: Disease Mechanisms and Therapies. Biomed. Res. Int., 2015:456348

32. Yu X, Bao B, Echigoya Y, Yokota T. (2015) Dystrophin-deficient large animal models: translational research and exon skipping. Am J Transl Res. 7(8):1214-31.

31. Nichols B, Takeda S, Yokota T. (2015) Nonmechanical roles of dystrophin and associated proteins in exercise, neuromuscular junctions, and brains. Brain Sci. 5: 275-298.

30. Echigoya Y, Mouly V, Garcia L, Yokota T (corresponding), Duddy W. (2015) In silico screening based on predictive algorithms as a design tool for exon skipping oligonucleotides in Duchenne muscular dystrophy. PLoS ONE 10(3): e0120058

29. Echigoya Y, Aoki Y, Miskew B, Panesar D, Touznik A, Nagata T, Tanihata J, Nakamura A, Nagaraju K, Yokota T. (2015) Long-term efficacy of systemic multi-exon skipping targeting dystrophin exons 45-55 with a cocktail of vivo-morpholinos in mdx52 mice. Mol. Ther. Nucleic Acids. 4: e225.

28. Bao B, Yokota T. (2015) Potential of antisense therapy for facioscapulohumeral muscular dystrophy. Expert Opin Orphan Drugs. 3(12):1365-1374.

27. Echigoya Y, Yokota T. (2014) Skipping multiple exons of dystrophin transcripts using cocktail antisense oligonucleotides. Nucleic Acid Ther., 24(1):57-68.

26. Pandey SN, Lee YC, Yokota T, Chen YW. (2014) Morpholino treatment improves muscle function and pathology of Pitx1 transgenic mice. Mol. Ther., 22(2):390-6.

25. Yokota T, Miyagoe-Suzuki Y, Ikemoto T, Takeda S. (2014) Alpha1-Syntrophin deficient mice exhibit impaired muscle force recovery after osmotic shock. Muscle Nerve, 49(5):728-35

24. Touznik A, Lee J, Yokota T. (2014) New developments in exon skipping and splice modulation therapy for neuromuscular diseases. Expert Opin. Biol. Ther. 14(6):809-19

23. Aoki Y, Nagata T, Yokota T, Nakamura A, Wood MJ, Partridge T, Takeda S. (2013) Highly efficient in vivo delivery of PMO into regenerating myotubes and rescue in laminin α2 chain-null congenital muscular dystrophy mice. Hum. Mol. Genet., 22(24):4914-28.

22. Lee J, Yokota T. (2013) Antisense therapy in neurology. J. Pers. Med. 3, 144-176

21. Echigoya Y*, Lee J*, Rodrigues M* (*equally contributed), Nagata T, Tanihata J, Nozohourmehrabad A, Panesar D, Miskew B, Aoki Y, Yokota T. (2013) Mutation Types and Aging Differently Affect Revertant Fiber Expansion in Dystrophic Mdx and Mdx52 Mice. PLoS One. 8(7):e69194.

20. Aoki Y, Yokota T, Wood MJ. (2013) Development of multiexon-skipping antisense oligonucleotide therapy for Duchenne muscular dystrophy. Biomed. Res. Int., 2013, 402369.

19. Aoki Y, Yokota T (corresponding), Nagata T, Nakamura A, Tanihata J, Saito T, Duguez SMR, Nagaraju K, Hoffman EP, Partridge T, Takeda S. (2012) Bodywide skipping of exons 45-55 in dystrophic mdx52 mice by systemic antisense delivery. Proc. Natl. Acad. Sci. U S A., 109(34):13763-8.

18. Yokota T (corresponding), Duddy W, Echigoya Y, Kolski H. (2012) Exon skipping for nonsense mutations in Duchenne muscular dystrophy: Too many mutations, too few patients? Expert Opin. Biol. Ther., 12(9):1141-52.

17. Yokota T (corresponding), Nakamura A, Nagata T, Saito T, Kobayashi M, Aoki Y, Echigoya Y, Partridge T, Hoffman E, Takeda S. (2012) Extensive and prolonged restoration of dystrophin expression with vivo-morpholino-mediated multiple exon skipping in dystrophic dogs. Nucleic Acid Ther., 22(5):306-15. *Featured Article

16. Hoffman EP, Bronson A, Baudy AR, Yokota T, Takeda S, Connor EM. (2011) Restoring dystrophin expression in Duchenne muscular dystrophy muscle: Progress in exon-skipping and stop codon read-through. Am. J. Pathol.,179(1):12-22.

15. Taniguchi M, Kobayashi M, Kanagawa M, Yu C, Mori K, Oda T, Kuga A, Kurahashi H, Akman HO, Di Mauro S, Kaji R, Yokota T, Takeda S, Toda T. (2011) Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy. Nature, 478:127-131.* Faculty of 1000 recommended paper (Factor 6) selection

14. Lu QL, Yokota T, Takeda S, Garcia L, Muntoni F, Partridge T. (2011) The status of exon skipping as a therapeutic approach to Duchenne muscular dystrophy, Mol. Ther.,19:9-15.

13. Aoki Y, Nakamura A, Yokota T, Saito T, Okazawa H, Nagata T, Takeda S. (2010) In-frame dystrophin following exon 51-skipping improves muscle pathology and function in the exon 52-deficient mdx mouse. Mol. Ther., 18:1995-2005.

12. Saito T, Nakamura A, Aoki Y, Yokota T, Okada T, Osawa M, Takeda S. (2010) Antisense PMO found in dystrophic dog model was effective in cells from exon 7-deleted DMD patient. PLoS One, 2010; 5:e12239.

11. Yokota T, Lu QL, Partridge T, Kobayashi M, Nakamura A, Takeda S, Hoffman E. (2009) Efficacy of morpholino systemic exon-skipping in Duchenne dystrophy dogs. Ann. Neurol., 65:667-76. * Faculty of 1000 exceptional paper (Factor 10) selection

10. Yokota T, Takeda S, Lu QL, Partridge T, Nakamura A, Hoffman E. (2009) *A renaissance for antisense oligonucleotide drugs in neurology: Exon-skipping breaks new ground. JAMA Neurol (Formerly Arch. Neurol.), 66:32-8. *Cover image selection

9. Sato K, Yokota T, Ichioka S, Shibata M, Takeda S. (2008) Vasodilation of intramuscular arterioles under shear stress in dystrophin-deficient skeletal muscle is impaired through decreased nNOS expression. Acta Myol., 27:30-6.

8. Yokota T (corresponding), Duddy W, Partridge T. (2007) Optimizing exon skipping therapies for DMD, Acta Myol.,26:179-84.

7. Yokota T (corresponding), Emidio P, Duddy W, Kanneboyina N. (2007) Potential of exon skipping therapy for Duchenne muscular dystrophy, Expert Opin. Biol. Ther., 7:831-42.

6. Yokota T, Lu QL, Morgan JE, Davies KE, Fisher R, Takeda S, Partridge T. (2006) Expansion of revertant fibers in dystrophic mdx muscles reflects activity of muscle precursor cells and serves as index of muscle regeneration. J. Cell Sci., 119: 2679-87.

5. Lu QL, Rabinowitz A, Chen YC, Yokota T, Yin H, Alter J, Jadoon A, Bou-Gharios G, Partridge T. (2005) Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal muscles. Proc. Natl. Acad. Sci. U S A., 102:198-203. *Cover image selection

4. Munehira Y, Ohnishi T, Kawamoto S, Furuya A, Shitara K, Imamura M, Yokota T, Takeda S, Amachi T, Matsuo M, Kioka N, Ueda K. (2004) Alpha1-syntrophin modulates turnover of ABCA1. J. Biol. Chem., 9; 279:15091-5.

3. Yokota T*, Hosaka Y* (*Equally Contributed), Miyagoe-Suzuki Y, Yuasa K, Imamura M, Matsuda R, Ikemoto T, Kameya S, Takeda S. (2002) Alpha1-syntrophin-deficient skeletal muscle exhibits hypertrophy and aberrant formation of neuromuscular junctions during regeneration, J. Cell Biol., 158: 1097-1107.

2. Sakamoto M, Yuasa K, Yoshimura M, Yokota T, Ikemoto T, Suzuki M, Dickson G, Miyagoe-Suzuki Y, Takeda S. (2002) Micro-dystrophin cDNA ameliorates dystrophic phenotypes when introduced into mdx mice as a transgene, Biochem. Biophys. Res. Commun., 293:1265-1272.

1. Yokota T, Hosaka Y, Tsukita K, Kameya S, Shibuya S, Matsuda R, Wakayama Y, Takeda S. (2000) Aquaporin-4 is absent at the sarcolemma and at perivascular astrocyte endfeet in alpha1-syntrophin knockout mice, Proc. Jpn. Acad. 76B:22-27.

b) Preprints

2. Nguyen Q, Lim KRQ, Yokota T. Genome Editing for the Understanding and Treatment of Cardiomyopathies. Preprints 2019, 2019120385 (doi: 10.20944/preprints201912.0385.v1).

1. Lim KRQ, Yoon C, Yokota T. Methods of CRISPR/Cas9 Exon Skipping for Duchenne Muscular Dystrophy. Preprints 2018, 2018110018 (doi: 10.20944/preprints201811.0018.v1).

c) Book Chapters

21. Goodkey K, Aslesh T, Maruyama R, Yokota T. (2018) Nusinersen in the treatment of spinal muscular atrophy.Methods Mol. Biol. 1828:69-76.

20. Touznik A, Maruyama R, Yokota T. In Vitro Evaluation of Antisense-Mediated Exon Inclusion for Spinal Muscular Atrophy. Methods Mol. Biol. 1828:439-454.

19. Rodrigues M, Yokota T. (2018) An Overview of Recent Advances and Clinical Applications of Exon Skipping and Splice Modulation for Muscular Dystrophy and Various Genetic Diseases. Methods Mol. Biol. 1828:31-55.

18. Lim K, Yokota T. (2018) Invention and early history of exon skipping and splice modulation. Methods Mol. Biol.1828:3-30.

17. Maruyama R, Yokota T. (2018) Tips to design splice-switching oligonucleotides for exon skipping and exon inclusion.Methods Mol. Biol. 1828:79-90.

16. Hara Y, Mizobe Y, Miyatake S, Takizawa H, Nagata T, Yokota T, Takeda S,Aoki Y. (2018) Exon skipping using antisense oligonucleotides for laminin-alpha2-deficient muscular dystrophy. Methods Mol. Biol. 1828:553-564.

15. Mizobe Y, Miyatake S, Takizawa H, Hara Y, Yokota T, Nakamura A, Takeda S,Aoki Y. (2018) In vivo evaluation of single- and multi-exon skipping in mdx52 mice. Methods Mol. Biol. 1828:275-292.

14. Melo D, Yokota T. (2018) Systemic injection of peptide-PMOs and evaluation by RT-PCR and ELISA. Methods Mol. Biol. 1828:263-273.

13. Maruyama R, Aoki Y, Takeda S, Yokota T. (2018) In Vivo Evaluation of Multiple Exon Skipping with Peptide-PMOs in Cardiac and Skeletal Muscles in Dystrophic Dogs. Methods Mol. Biol. 1828:365-379.

12. Son H, Yokota T. (2018) Recent advances and clinical applications of exon inclusion for SMA. Methods Mol. Biol. 1828:57-68.

11. Maruyama R, Yokota T. (2018)Morpholino-mediated exon skipping targeting human ACVR1/ALK2 for fibrodysplasia ossificans progressiva. Methods Mol. Biol. 1828:497-502.

10. Lim K, Yokota T. (2018) Quantitative evaluation of exon skipping in immortalized muscle cells in vitro. Methods Mol. Biol. 1828:127-139.

9. Aslesh T, Maruyama R, Yokota T. (2018) Systemic and ICV injections of antisense oligos into SMA mice and evaluation. Methods Mol. Biol. 1828:455-465.

8. Lee JJA, Saito T, Duddy W, Takeda S, Yokota T. (2018) Direct reprogramming of human DMD fibroblasts into myotubes for in vitro evaluation of antisense-mediated exon skipping and exons 45-55 skipping accompanied by rescue of dystrophin expression. Methods Mol. Biol. 1828:141-150.

7. Maruyama R, Yokota T. (2018) Creation of DMD muscle cell model using CRISPR-Cas9 genome editing to test the efficacy of exon skipping. Methods Mol. Biol. 1828:165-171.

6. Nakamura A, Aoki Y, Tsoumpra M, Yokota T, Takeda S. (2018) In vitro Multi-exon Skipping by Antisense PMOs in Dystrophic Dog and Exon 7-Deleted DMD Patient. Methods Mol. Biol. 1828:151-163.

5. Miyatake S, Mizobe Y, Takizawa H, Hara Y, Yokota T, Takeda S,Aoki Y. (2018) Exon skipping therapy using phosphorodiamidate morpholino oligomers in the mdx52 mouse model of Duchenne muscular dystrophy. Methods Mol. Biol. 1687:123-141.

4. Shimo T, Maruyama R, Yokota T. (2018) Designing effective antisense oligonucleotides for exon skipping. Methods Mol. Biol. 1687:143-155.

3. Maruyama R, Echigoya Y, Caluseriu O, Aoki Y, Takeda S, Yokota T. (2017) Systemic Delivery of Morpholinos to Skip Multiple Exons in a Dog Model of Duchenne Muscular Dystrophy. Methods Mol. Biol.1565:201-213.

2. Lee JJA, Yokota T. (2016) Translational research in nucleic acid therapies for muscular dystrophies. In Translational Research in Muscular Dystrophy (pp. 87-102), DOI: 10.1007/978-4-431-55678-7 © Springer., Tokyo, Japan

1. Yokota T (corresponding), Hoffman E, Takeda S. (2011) Antisense oligo-mediated multi-exon-skipping in a dog model of Duchenne muscular dystrophy. Methods Mol. Biol. 709;299-312.

d) Books

1. Yokota T and Maruyama R (Eds). (2018) Exon Skipping and Inclusion Therapies- Methods in Molecular Biology, Springer-Nature, ISBN: 978-1-4939-8650-7.

Complete List of Published Work in My Bibliography:

The laboratory of Dr. Toshifumi Yokota invites applications for postdoc, undergraduate and graduate student positions. By utilizing integrative experimental and computational approaches, such as antisense oligonucleotides, CRISPR/Cas9, and machine-learning, the focuses of his group are to develop novel molecular therapies for neuromuscular and musculoskeletal diseases. These new methods are applied to the correction of genetic mutations, new disease models, drug discovery, and addressing fundamental biological questions. His group is actively collaborating with the world-class researchers and industry partners. The highly interdisciplinary and collaborative environment provides unique career development opportunities for trainees. His laboratory is renowned internationally for its work on the development of genome-editing/antisense technology as well as the studies on animal models. His studies led to the development of viltolarsen, an antisense oligonucleotide drug to treat Duchenne muscular dystrophy, which was approved in Japan in 2020 and is currently under review for FDA approval. He edited 2 protocol books on antisense-mediated exon skipping/inclusion and RNase H-inducing oligonucleotides called gapmers (Exon Skipping and Inclusion Therapies. Methods. Mol. Biol., 2018; Gapmers. Methods. Mol. Biol., 2020. Springer-Nature). Full-time graduate students receive a stipend guaranteed to be equal to or greater than the minimum, determined yearly by the graduate committee (approximately $24,000-25,000/year). Priority will be given to those who want to further pursue PhD degree.

Representative original research publications of the PI with trainees since 2016 include;
1. Echigoya et al (2019) Mol Ther. 27:2005–2017 (IF=8.402)
2. Lim et al (2019) Mol Ther. 27: 76-86
3. Lee et al (2018) Mol Ther Nucleic Acids.13: 596-604 (IF=5.919)
4. Lee et al (2018) PLoS ONE.13:e0197084 (IF=3.057)
5. Echigoya et al (2017) PNAS. 114:4213-8 (IF=9.580)
6. Echigoya et al (2017) Mol Ther. 25: 2561-2572
7. Touznik et al (2017) Sci Rep. 7:3672 (IF=4.259)
8. Kamaludin et al (2016) Hum. Mol. Genet., 25(17):3798-3809.(IF=6.393)
9. Rodrigues et al (2016) Sci. Rep., 6, 38371
(trainees underlined)

Each trainee receives training in a variety of areas, acquiring a basic skill set they need to further their individual projects. These skills include in silico drug design, muscle cell culture (human and animal cells), animal models (mice, dogs, and pigs), muscle physiology (e.g. exercise studies, grip strength, and in vitro muscle force measurement), histology, molecular analysis (e.g. RNA-seq, quantitative real-time reverse transcription PCR analysis, molecular cloning), protein biochemistry, and proteomics analysis. This will ensure successful academic research careers and/or other career paths in non-academic health-related fields. Past members have landed faculty positions in universities (e.g. Nihon University, University of Vermont) and jobs in the life science industry (e.g. Eli Lilly).

Located in Edmonton, one of the sunniest cities in Canada, the Faculty has been internationally recognized as among the world’s top 50 medical schools and as one of Canada’s premier health-education institutions. The University is currently home to 39,000 students and 15,000 faculty and staff.

All applicants should have good spoken and written communication skills in English. Interested applicants should send i) a cover letter briefly describing your previous experience and your future research interest/plan, ii) a curriculum vitae, and iii) contact information of at least three references to Dr. Toshifumi Yokota (

Rika Maruyama - Research Associate
Stanley Woo - LabTechnician
Kenji Lim - Graduate Student
Tejal Aslesh - Graduate Student
Rohini Roshmi - Undergraduate Student
Isabella Huang - Undergraduate Student
Kasia Dzierlega - Undergraduate Student
Leanna Chan - Undergraduate Student
Maria Mahfouz - Undergraduate Student