PDF file: EURASNET Annual Report 2008

Participant 13 – Daniel Schümperlia) Work performed during the periodWP14• The group has completed a study and published a paper on a triple antisense vector toinhibit HIV-1 replication (Ref 1; in collaboration with D. Trono and coworkers, EPFLLausanne, Switzerland).• Another short paper emerged from a fruitful collaboration with the group of C. Leumann,University of Bern on the use of tricyclo-DNA oligonucleotides (Ref. 2).• Moreover the U7-based methods to induce exon inclusion in the survival of motoneuron 2gene (SMN2) have been tested by transgenesis in a severe mouse model for SpinalMuscular Atrophy (SMA). Survival of SMA affected mice could be prolonged from 1week wwithout to a median of 5 months with the therapeutic U7 gene. In some mice,weight development, muscle performance, female fertility and longevity were absolutelynormal. The study was published online in 2008 and in printed form in 2009 (Ref. 3).• The development and characterisation of inducible U7 snRNA cassettes has beencompleted and published (Ref. 4).Publications:1. Asparuhova MB, Barde I, Trono D, Schranz K, Schümperli D. (2008) Development andcharacterization of a triple combination gene therapy vector inhibiting HIV-1multiplication. J Gene Med. 10, 1059-1070.2. Ittig, D., Schümperli, D. and Leumann, C.J. (2008) Tc-DNA modified siRNA. NucleicAcids Symp Ser (Oxf). 52, 501-502.3. Meyer, K., Marquis, J., Trüb, J., Nlend Nlend, R., Verp, S., Ruepp, M.-D., Imboden, H.,Barde, I., Trono, D. and Schümperli, D. (2009) Rescue of a severe mouse model forSpinal Muscular Atrophy by U7 snRNA-mediated splicing modulation. Hum. Mol.Genet. 18, 546-555. Epub 2008 Nov 13.4. Marquis, J., Kämpfer, S.S., Angehrn, L. and Schümperli, D. (2009) Doxycyclinecontrolledsplicing modulation by regulated antisense U7 snRNA expression cassettes.Gene Ther. 16, 70-77. Epub 2008 Aug 14.WP20• As mentioned last year participant 13 is collaborating with the groups of Prof. ChristianLeumann, Department of Chemistry and Biochemistry, University of Bern, and that ofDr. Luis Garcia, Institut de Myologie Paris, France, on tricyclo-DNA applications to exonskipping in Duchenne Muscular Dystrophy (DMD). The tricyclo-DNA chemistry itself isno longer patentable, again for reasons of prior disclosure, but the collaborating groupshope to obtain a patent for the special application of their technology to DMD.b) Major cost items with justificationParticipant 1A Type of expenditure Budget total costspersonnelconsumables 52.364,00trainingequipmenttravel= total direct costs 52.364,00+ overhead 10.472,80= total eligible costs 62.836,80163