Toshifumi (Toshi) Yokota () is a

biomedical scientist A biomedical scientist is a scientist trained in biology, particularly in the context of medical laboratory sciences or laboratory medicine. These scientists work to gain knowledge on the main principles of how the human body works and to find new ...

and professor of medical genetics at the

University of Alberta The University of Alberta (also known as U of A or UAlberta, ) is a public research university located in Edmonton, Alberta, Canada. It was founded in 1908 by Alexander Cameron Rutherford, the first premier of Alberta, and Henry Marshall Tory, t ...

, holding the titles of the Friends of Garrett Cumming Research & Muscular Dystrophy Canada Endowed Research Chair and the Henri M. Toupin Chair in Neurological Science. Yokota is widely recognized for pioneering work in

antisense therapy Antisense therapy is a form of treatment that uses antisense oligonucleotides (ASOs) to target messenger RNA (mRNA). ASOs are capable of altering mRNA expression through a variety of mechanisms, including ribonuclease H mediated decay of the pre-m ...

for

muscular dystrophy Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily affe ...

and other

genetic diseases A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosome abnormality. Although polygenic disorders are ...

, which led to the development of

viltolarsen Viltolarsen, sold under the brand name Viltepso, is a medication used for the treatment of Duchenne muscular dystrophy (DMD). Viltolarsen is a Morpholino antisense oligonucleotide. The most common side effects include upper respiratory tract in ...

, an FDA-approved treatment for

Duchenne muscular dystrophy Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy predominantly affecting boys. The onset of muscle weakness typically begins around age four, with rapid progression. Initially, muscle loss occurs in the thighs and pe ...

(DMD). With over 100 peer-reviewed publications and several patents, Yokota has made significant contributions to the field of

precision medicine Precision, precise or precisely may refer to: Arts and media * ''Precision'' (march), the official marching music of the Royal Military College of Canada * "Precision" (song), by Big Sean * ''Precisely'' (sketch), a dramatic sketch by the Eng ...

. Yokota also co-edited three volumes in the

Methods in Molecular Biology ''Methods in Molecular Biology'' is a book series published by Humana Press (an imprint of Springer Science+Business Media) that covers molecular biology research methods and protocols. The book series was introduced by series editor John M. Walke ...

series by

Humana Press Humana Press was an American academic publisher of science, technology, and medical books and journals founded in 1976. It was bought by Springer Science+Business Media in 2006. History Humana published more than 100 new books and 25 journal ...

, Springer-Nature and is on editorial boards of multiple scientific journals. In 2023, Yokota was elected as a fellow of the

Canadian Academy of Health Sciences The Canadian Academy of Health Sciences (CAHS) is one of three national academies that comprise the Council of Canadian Academies (CCA), the highest honour granted to scholars in Canada. The two other CCA academies are the Royal Society of Cana ...

, an honor that recognizes outstanding achievements in health sciences. In addition, Yokota is Chief Scientific Officer at OligomicsTx, is a co-founder of the Canadian Neuromuscular Network (CAN-NMD), and contributes as a member of the Medical and Scientific Advisory Committee of Muscular Dystrophy Canada.

Biography

Yokota was born in

Morioka is the capital Cities of Japan, city of Iwate Prefecture located in the Tōhoku region of northern Japan. On 1 August 2023, the city had an estimated population of 283,981 in 132,719 households, and a population density of . The total area of t ...

, a city in

Iwate Prefecture is a Prefectures of Japan, prefecture of Japan located in the Tōhoku region of Honshu. It is the second-largest Japanese prefecture (behind Hokkaido) at , with a population of 1,165,886 (as of July 1, 2023). Iwate Prefecture borders Aomori Pre ...

, and raised in multiple cities including

Tsu, Mie is the capital city of Mie Prefecture, Japan. , the city had an estimated population of 274,879 in 127,273 households and a population density of 390 persons per km2. The total area of the city is . Although the second largest city in the ...

and

Nerima is a Special wards of Tokyo, special ward in the Tokyo, Tokyo Metropolis in Japan. The ward refers to itself as Nerima City. , the ward has an estimated population of 721,858, with 323,296 households and a population density of 15,013 persons ...

, Tokyo, in Japan. After completing a Ph.D. in

Biological Science Biology is the scientific study of life and living organisms. It is a broad natural science that encompasses a wide range of fields and unifying principles that explain the structure, function, growth, origin, evolution, and distribution of ...

in 2003, further training was undertaken at

Imperial College London Imperial College London, also known as Imperial, is a Public university, public research university in London, England. Its history began with Prince Albert of Saxe-Coburg and Gotha, Prince Albert, husband of Queen Victoria, who envisioned a Al ...

, as a Research Fellow of the

Japan Society for the Promotion of Science The is an Independent Administrative Institution in Japan, established for the purpose of contributing to the advancement of science in all fields of the natural and social sciences and the humanities.JSPSweb page History The Japan Society f ...

, and as a Research Associate at the

Children's National Medical Center Children's National Hospital (formerly Children's National Health System, DC Children's Hospital, Children's National Medical Center) is a freestanding, 323-bed, pediatric acute care children's hospital located in Washington, D.C. It is affili ...

before joining the University of Alberta in 2011. Yokota is a tenured professor at the

University of Alberta Faculty of Medicine and Dentistry The Faculty of Medicine and Dentistry at University of Alberta is located in Edmonton, Alberta, Canada. Established in 1913, it is one of the oldest medical schools in Western Canada and is composed of 21 departments, two stand-alone divisions, 9 ...

, and the Friends of Garrett Cumming Research & Muscular Dystrophy Canada Endowed Research Chair and the Henri M. Toupin Chair in Neurological Science since 2011. In 2022, Yokota received the Scientific Achievement and Innovation Award from BioAlberta. In 2023, Yokota was elected as a Fellow of the

Major contributions

Yokota's research focuses on precision health and personalized genetic medicine using single strands of artificial DNA/RNA-like molecules called antisense oligonucleotides for

neuromuscular disease A neuromuscular disease is any disease affecting the peripheral nervous system (PNS), the neuromuscular junctions, or skeletal muscles, all of which are components of the motor unit. Damage to any of these structures can cause muscle atrophy and we ...

s. Yokota demonstrated the therapeutic potential of antisense oligonucleotides for

exon skipping In molecular biology, exon skipping is a form of RNA splicing used to cause cells to “skip” over faulty or misaligned sections (exons) of genetic code, leading to a truncated but still functional protein despite the genetic mutation. Mechanis ...

, which can be designed to frame-disrupting

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...

s and restore the

reading frame In molecular biology, a reading frame is a specific choice out of the possible ways to read the nucleic acid sequence, sequence of nucleotides in a nucleic acid (DNA or RNA) molecule as a sequence of triplets. Where these triplets equate to amino ...

and function of a mutated

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

by modulating

pre-mRNA A primary transcript is the single-stranded ribonucleic acid (RNA) product synthesized by Transcription (genetics), transcription of DNA, and processed to yield various mature RNA products such as mRNAs, tRNAs, and rRNAs. The primary transcript ...

splicing, leading to the improvement of skeletal muscle function accompanied by

dystrophin Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the costa ...

restoration for the first time in a severe animal model of

(DMD). Based on the study,

, a phosphorodiamidate morpholino oligomer antisense oligonucleotide, was developed for the treatment of DMD in collaboration with a Japanese pharmaceutical company. Viltolarsen was later approved by the

Pharmaceuticals and Medical Devices Agency The (PMDA) is a Japanese corporation, an Independent Administrative Institution, responsible for ensuring the safety, efficacy and quality of pharmaceuticals and medical devices in Japan. It is similar in function, in many respects, to the Foo ...

in Japan and by the

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

in the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

in March and August 2020, respectively, after clinical trials conducted in Japan,

Canada Canada is a country in North America. Its Provinces and territories of Canada, ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, making it the world's List of coun ...

, and the United States. Yokota's team further developed a potential treatment for nearly half of DMD patients using multiple antisense oligonucleotides and demonstrated therapeutic effects in a dystrophic mouse model. Supported by the

Heart and Stroke Foundation of Canada The Heart and Stroke Foundation of Canada is a Canadian charity dedicated to advocacy, education, and the funding of research surrounding heart disease and stroke. Nomenclature In November 2016, the organization re-branded as Heart & Stroke a ...

, the research team developed a cocktail of peptide-conjugated morpholinos (PPMOs) and restored expression of dystrophin in the myocardium and Purkinje fibers in the heart muscle of dystrophic animal models. In 2021, the team developed eSkip-Finder, a

machine learning Machine learning (ML) is a field of study in artificial intelligence concerned with the development and study of Computational statistics, statistical algorithms that can learn from data and generalise to unseen data, and thus perform Task ( ...

-mediated free online application with a database of antisense oligonucleotides to facilitate the design of antisense oligonucleotides that can be used for exon skipping targeted for various genes and exons. Supported by the

Canadian Institutes of Health Research The Canadian Institutes of Health Research (CIHR; ; IRSC) is a federal agency responsible for funding health and medical research in Canada. Comprising 13 institutes, it is the successor to the Medical Research Council of Canada. CIHR supports ...

and Muscular Dystrophy Canada, Yokota's team is also developing antisense oligonucleotide-mediated therapy for

facioscapulohumeral muscular dystrophy Facioscapulohumeral muscular dystrophy (FSHD) is a type of muscular dystrophy, a group of heritable diseases that cause degeneration of muscle and progressive weakness. Per the name, FSHD tends to sequentially weaken the muscles of the fac ...

using

lipid nanoparticle Lipid-based nanoparticles are very small spherical particles composed of lipids. They are a novel pharmaceutical drug delivery system (part of nanoparticle drug delivery), and a novel pharmaceutical formulation. There are many subclasses of ...

s in collaboration with Pieter Cullis. In 2020, they identified antisense oligonucleotides called gapmers that knock down the expression of a toxic gene called DUX4 in cell and mouse models for the treatment of facioscapulohumeral muscular dystrophy. Yokota’s research identified ASO targets for skipping multiple dysferlin (DYSF) exons (26-27 and 28-29), which were shown to enhance membrane resealing function in patient cells—a therapeutic approach applicable to 5-8% of dysferlinopathy patients globally. In 2022, Yokota's team identified gapmers that selectively knocked down most of the mutated

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

for the treatment of

fibrodysplasia ossificans progressiva Fibrodysplasia ossificans progressiva (; FOP), also called Münchmeyer disease or formerly myositis ossificans progressiva, is an extremely rare connective tissue disease in which fibrous connective tissue such as muscle, tendons, and ligamen ...

. With support from

CIHR The Canadian Institutes of Health Research (CIHR; ; IRSC) is a federal agency responsible for funding health and medical research in Canada. Comprising 13 institutes, it is the successor to the Medical Research Council of Canada. CIHR supports ...

and muscular dystrophy Canada, the team also identified novel peptide-conjugated morpholinos called DG9-PMOs that effectively improved mouse models of DMD and

spinal muscular atrophy Spinal muscular atrophy (SMA) is a rare neuromuscular disorder that results in the loss of motor neurons and progressive muscle wasting. It is usually diagnosed in infancy or early childhood and if left untreated it is the most common geneti ...

Patient advocacy

In addition to research achievements, Yokota has significantly advanced patient advocacy in the realm of genetic disorders, particularly muscular dystrophy. Advocacy efforts are strongly reflected in the integration of individuals affected by muscular dystrophy into the research team, which enhances the research approach with valuable firsthand insights. This initiative aligns with Yokota’s broader dedication to equity, diversity, and inclusion (EDI), actively seeking to bring diverse perspectives into the scientific process.

Honors

Yokota is honored as a ScholarGPS Highly Ranked Scholar. Yokota's publication record, impact of work, and quality of scholarly contributions have earned rankings of first in

Muscular dystrophy Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily affe ...

, third in

Oligonucleotide Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, Recombinant DNA, research, and Forensic DNA, forensics. Commonly made in the laboratory by Oligonucleotide synthesis, solid-phase ...

, and third in Personalized medicine globally over the last five years, placing in the top 0.01 percent of highly ranked scholars. * Research Fellow of the Japan Society for the Promotion of Science (2003-2005) *

National Institutes of Health The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Service ...

Ruth L. Kirschstein

National Research Service Award The Ruth L. Kirschstein National Research Service Awards (usually referred to as NRSA) are a family of grants provided by the United States National Institutes of Health (NIH) for training researchers in the behavioral sciences and health sciences. ...

(2010) * The Friends of Garrett Cumming Research & Muscular Dystrophy Canada Endowed Research Chair (2011-) * The Henri M. Toupin Chair in Neurological Science (2011-) * Canadian Institutes of Health Research China-Canada Joint Health Research Initiative Award (2013) * Scientific Achievement and Innovation Award, BioAlberta (2022) * Fellow of the Canadian Academy of Health Sciences (2023) * Startup TNT Life Sciences Summit Finale Pitch Night Winner (2024) * University of Alberta Innovation Award (2024)

Selected publications

* Yokota T, Lu QL, Partridge T, Kobayashi M, Nakamura A, Takeda S, Hoffman E. Efficacy of morpholino systemic exon-skipping in Duchenne dystrophy dogs
Ann. Neurol., 2009, 65:667-76.
* 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. Quantitative antisense screening and optimization for exon 51 skipping in Duchenne muscular dystrophy
Mol Ther. 2017, 25(11): 2561-2572.
* 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. 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., 2017, 114 (16), 4213-4218.
* Lim K, Echigoya Y, Nagata T, Kuraoka M, Kobayashi M, Aoki Y, Partridge T, Maruyama R, Takeda S, Yokota T. Efficacy of multi-exon skipping treatment in Duchenne muscular dystrophy dog model neonates
Mol. Ther. 2019, 27(1): 76-86.
* Echigoya Y, Lim K, Melo D, Bao B, Trieu N, Mizobe Y, Maruyama R, Mamchaoui K, Tanihata J, Aoki Y, Takeda S, Mouly V, Duddy W, Yokota T. Exons 45-55 skipping using mutation-tailored cocktails of antisense morpholinos in the DMD gene
Mol. Ther. 2019, 27(11): 2005-17.
* Lim K, Maruyama R, Echigoya Y, Nguyen Q, Khawaja H, Chandra S, Jones T, Jones P, Chen Y, Yokota T. Inhibition of DUX4 expression with antisense LNA gapmers as a therapy for facioscapulohumeral muscular dystrophy
Proc. Natl. Acad. Sci. U S A. 2020, 117 (28), 16509-16515.
* Lim K, Bittel A, Maruyama R, Echigoya Y, Nguyen Q, Huang Y, Dzierlega, Zhang A, Chen Y, Yokota T. DUX4 transcript knockdown with antisense 2’-O-methoxyethyl gapmers for the treatment of facioscapulohumeral muscular dystrophy
Mol. Ther. 2021, 29(2): 848-58.
* Chiba S, Lim K, Sheri N, Anwar S, Erkut E, Shah A, Aslesh T, Woo S, Sheikh O, Maruyama R, Takano H, Kunitake K, Duddy W, Okuno Y, Aoki Y, Yokota T. eSkip-Finder: a machine learning-based web application and database to identify the optimal sequences of antisense oligonucleotides for exon skipping
Nucleic Acids Res. 2021, 49(W1):W193-W198.
* Lim K, Woo S, Melo D, Huang Y, Dzierlega K, Shah MNA, Aslesh, Roshmi RR, Echigoya Y, Maruyama R, Moulton HM, Yokota T. Development of DG9 peptide-conjugated single- and multi-exon skipping therapies for the treatment of Duchenne muscular dystrophy
Proc. Natl. Acad. Sci. U S A. 2022, 119 (9) e2112546119.
* Aslesh T, Erkut E, Ren J, Lim KRQ, Woo S, Hatlevig S, Moulton HM , Gosgnach S, Greer J , Maruyama R, Yokota T. DG9 peptide-conjugated morpholino rescues phenotype in SMA model mice by reaching the CNS through a single subcutaneous administration
JCI Insight.2023, e160516
* Anwar S, Roshmi RR, Woo S, Haque US, Lee J, Duddy WJ, Bigot A, Maruyama R, Yokota T. Antisense oligonucleotide-mediated exon 27 skipping restores dysferlin function in dysferlinopathy patient-derived muscle cells
Mol Ther Nucleic Acids. 2025, 36(1):102443.

References

External links

Yokota Laboratory
* {{DEFAULTSORT:Yokota, Toshifumi Japanese medical researchers Living people Year of birth missing (living people) University of Tokyo alumni Academic staff of the University of Alberta People from Morioka, Iwate 21st-century Japanese biologists Japanese expatriates in the United Kingdom People from Nerima People from Tsu, Mie Japanese geneticists Japanese expatriates in Canada Japanese neuroscientists Scientists from Iwate Prefecture Scientists from Mie Prefecture Scientists from Tokyo