Dr. Annemieke Aartsma-Rus is an associate professor at the Department of Human Genetics of the LUMC. She studied Biomedical Science at the Leiden University from 1995 to 2000. As a PhD student at the Human Genetics Department (LUMC) from 2000-2005, she focused on the development of antisense-mediated exon skipping therapy for Duchenne muscular dystrophy, under supervision of Dr. Judith CT van Deutekom and Prof. Dr. Gert-Jan B van Ommen. She defended her Thesis "Development of an antisense-mediated exon skipping therapy for Duchenne muscular dystrophy – Making sense out of nonsense" on February 10th 2005. After obtaining her PhD she continued her work on the optimization of antisense-mediated exon skipping towards clinical application as a postdoc. Now that Judith van Deutekom is working with Prosensa B.V. (as of February 2007), Dr Aartsma-Rus took over as project leader of the DMD Genetic Therapy group.
Publication list
Aartsma-Rus,A., Bremmer-Bout,M., Janson,A., Den Dunnen,J., van Ommen,G., and van Deutekom,J. (2002) Targeted exon skipping as a potential gene correction therapy for Duchenne muscular dystrophy. Neuromuscul Disord, 12, S71-S77.
Aartsma-Rus,A., Janson,A.A., Kaman,W.E., Bremmer-Bout,M., den Dunnen,J.T., Baas,F., van Ommen,G.J., and van Deutekom,J.C. (2003) Therapeutic antisense-induced exon skipping in cultured muscle cells from six different DMD patients. Hum Mol Genet, 12, 907-14.
Aartsma-Rus,A., Janson,A.A., Kaman,W.E., Bremmer-Bout,M., van Ommen,G.J., den Dunnen,J.T., and van Deutekom,J.C. (2004) Antisense-induced multiexon skipping for duchenne muscular dystrophy makes more sense. Am J Hum Genet, 74, 83-92.
Aartsma-Rus, A., Kaman, W.E., Bremmer-Bout, M., Janson, A.A.M., Den Dunnen, J.T., Van Ommen, G-J.B., Van Deutekom, J.C.T. (2004) Comparative analysis of antisense oligonucleotide analogs for tageted DMD exon 46 skipping in muscle cells. Gene Therapy, 11, 1391-1398.
Bremmer-Bout,M., Aartsma-Rus, A., De Meijer, E.J. , Kaman, W.E., Janson, A.A.M, Vossen, R.H.A.M., Van Ommen, G-J.B., Den Dunnen, J.T., Van Deutekom, J.C.T. (2004) Targeted Exon Skipping in Transgenic hDMD Mice: a Model for Direct Pre-clinical Screening of Human-specific Antisense Oligonucleotides. Molecular Therapy, 10, 232-240.
Aartsma-Rus, A. Development of an antisense-mediated exon skipping
therapy for Duchenne Muscular Dystrophy; making sense out of nonsense.
10-2-2005. Leiden University Medical Center - Department of Human and
Clinical Genetics.
Aartsma-Rus,A., De Winter,C.L., Janson,A.A.,
Kaman,W.E., van Ommen,G.J., Den Dunnen,J.T., and van Deutekom,J.C. (2005)
Functional analysis of 114 exon-internal AONs for targeted DMD exon skipping:
indication for steric hindrance of SR protein binding sites. Oligonucleotides.,
15, 284-297.
't Hoen,P.A.,
van der Wees,C.G., Aartsma-Rus,A., Turk,R., Goyenvalle,A., Danos,O.,
Garcia,L., van Ommen,G.J., Den Dunnen,J.T., and van Deutekom,J.C. (2006) Gene
expression profiling to monitor therapeutic and adverse effects of antisense
therapies for Duchenne muscular dystrophy. Pharmacogenomics., 7,
281-297.
Aartsma-Rus,A., Janson,A.A., Heemskerk,J.A.,
De Winter,C.L., van Ommen,G.J., and van Deutekom,J.C. (2006) Therapeutic
modulation of DMD splicing by blocking exonic splicing enhancer sites with
antisense oligonucleotides. Ann.N.Y.Acad.Sci., 1082, 74-76.
Aartsma-Rus,A., van Deutekom,J.C.,
Fokkema,I.F., van Ommen,G.J., and Den Dunnen,J.T. (2006) Entries in the Leiden
Duchenne muscular dystrophy mutation database: an overview of mutation types and
paradoxical cases that confirm the reading-frame rule. Muscle Nerve,
34, 135-144.
Aartsma-Rus,A., Kaman,W.E., Weij,R., Den Dunnen,J.T., van Ommen,G.J., and
van Deutekom,J.C. (2006) Exploring the frontiers of therapeutic exon skipping
for Duchenne muscular dystrophy by double targeting within one or multiple exons.
Mol Ther, 14, 401-407.
White,S.J., Aartsma-Rus,A., Flanigan,K.M., Weiss,R.B., Kneppers,A.L.,
Lalic,T., Janson,A.A., Ginjaar,H.B., Breuning,M.H., and Den Dunnen,J.T. (2006)
Duplications in the DMD gene. Hum.Mutat., 27, 938-945.
Aartsma-Rus,A., Janson,A.A., van Ommen,G.J., and van Deutekom,J.C. (2007)
Antisense-induced exon skipping for duplications in Duchenne muscular dystrophy.
BMC.Med.Genet., 8, 43.
Aartsma-Rus,A., van Ommen,G.J. (2007) Antisense-mediated exon skipping: A
versatile tool with therapeutic and research applications. RNA. 13,1609-1624.
Arechavala-Gomeza, V., Graham, I.R., Popplewell, L.J., Adams, A.M.,
Aartsma-Rus, A., Kinali, M., Morgan, J.E., van Deutekom, J.C.T., Wilton, S.D.,
Dickson, G. and Muntoni, F. (2007) Comparative analysis of antisense
oligonucleotide sequences for targeted skipping of exon 51 during dystrophin
pre-mRNA splicing in human muscle. Hum Gen Ther, epub Sept 3.
Van Deutekom, J.C.T., Janson,
A.A.M., Ginjaar, H.B., Frankhuizen W.S., Aartsma-Rus, A., Bremmer-Bout,
M. den Dunnen, J.T., Koop, K., van der Kooi, A.J., Goemans, N.M., de Kimpe, S.J.,
Ekhart, P.F., Venneker, E.H., Platenburg, G.J., Verschuuren, J.J. and van Ommen,
G-J.B. (2007) Local dystrophin restoration with antisense oligonucleotide PRO051. N Engl J Med, 357:2677-86
De Winter, C.L. and
Aartsma-Rus, A. (2007) RNA-therapie voor de ziekte van Duchenne: Minder is
meer. Analyse 07: 192-196. (Anna Wichersprijs for best paper in
2007-2008).
Van Ommen, G-J.B., Van Deutekom, J.C.T. and Aartsma-Rus, A. (2008) The
therapeutic potential of antisense-mediated exon skipping. Curr Opin Mol Ther
10: 140-9.
Aartsma-Rus A, van Vliet L, Hirschi M et al. (2008) Guidelines
for antisense oligonucleotide design and insight in splice modulating
mechanisms. Mol Ther; 23 Sept 2008 Ebup
Van Vliet L, de Winter CL, van Deutekom
JCT....and Aartsma-Rus A (2008) Assessment of the feasibility of exon
45-55 multiexon skipping for Duchenne muscular dystrophy. BMC Med Genet,
9:105
Heemskerk JA, de Winter CL, De Kimpe S...and Aartsma-Rus A (2009)
In vivo comparison of 2'O-methyl-PS and morpholino antisense oligonucleotides
for DMD exon skipping. J Gene Med ;11:257-66
Aartsma-Rus A, Fokkema I, Verschuuren J,
Ginjaar HB et al. (2008): Applicability of antisense-mediated exon skipping for
Duchenne muscular dystrophy mutations. Human Mutation; 30:293-9
Aartsma-Rus A
and van Ommen G-JB: Less is more: therapeutic exon skipping for Duchenne
muscular dystrophy. Lancet Neurology 2009; August 25 epub.
Heemskerk JA, de Winter
CL, van Ommen G-J, van Deutekom JCT and Aartsma-Rus A:
Development of antisense-mediated exon skipping as
a treatment for Duchenne muscular dystrophy. Annals of the NY Acad Science 2009;
1175: 71-9.
Aartsma-Rus A and van Ommen GJB: Progress in
therapeutic antisense applications for neuromuscular disorders. European Journal
of Human Genetics 2010; 18: 146-53.
Popplewell LJ, Adkin C, Arechavala-Gomeza V, Aartsma-Rus A et al:
Comparative analysis of antisense oligonucleotide sequences targeting exon 53 of
the human DMD gene:
Implications for future clinical trials. Neuromuscular Disorders 2010; 20:
102-110.
Aartsma-Rus A, Singh KH, Fokkema IF, Ginjaar IB, van Ommen GJ, Dunnen JT, van der Maarel SM: Therapeutic exon skipping for dysferlinopathies? European Journal of Human Genetics; Feb 10 epub.
Helderman-van
den Enden AT,
Straathof CS,
Aartsma-Rus A et al: Becker muscular
dystrophy patients with deletions around exon 51; a promising outlook for exon
skipping therapy in Duchenne patients. Neuromuscular Disorders 2010;20: 251-4
Aartsma-Rus A and van Ommen GJB.
2010. Antisense-mediated exon skipping
for Duchenne muscular dystrophy. In Muscle Gene Therapy (Ed Duan, D) Springer
New York Dordrecht Heidelberg London. (ISBN: 978-1-4419-1205-3).
Van Putten M, Winter CL,
van Roon-Mom W, van Ommen G-JB, 't Hoen PAC and Aartsma-Rus A: A mild
exercise regime does not affect disease parameters in the mdx mouse.
Neuromuscular Disorders 2010; 20: 273-80
Aartsma-Rus A, Houlleberghs H, van Deutekom JCT, van Ommen G-J and 't
Hoen PAC: Exon-targeting antisense
oligonucleotides outperform splice site targeting antisense oligonucleotides in
the modulation of DMD splicing. Oligonucleotides 2010; Apr 6 epub
Heemskerk JA, de Winter CL, van Kuik P….Aartsma-Rus A, and van Deutekom JCT: Pre-clinical PK and PD Studies on 2’O-Methyl-Phosphorothioate RNA Antisense Oligonucleotides in the mdx mouse model. Mol Ther 2010; Apr 20 epub
Spitali P, Heemskerk JA, Vossen RHAM, Ferlini A, den Dunnen JT, 't Hoen PAC and Aartsma-Rus A: Accurate quantification of dystrophin mRNA and exon skipping levels in Duchenne Muscular Dystrophy. Lab Invest 2010; in press
Aartsma-Rus A: Antisense-mediated modulation of splicing: therapeutic implications for Duchenne muscular dystrophy. RNA Biology 2010; in press
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