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Nucleic Acid Ther. 2016 Dec;26(6):381-391. Epub 2016 Sep 15.

Four Novel Splice-Switch Reporter Cell Lines: Distinct Impact of Oligonucleotide Chemistry and Delivery Vector on Biological Activity.

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1 Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Karolinska University Hospital , Huddinge, Sweden .
2 Integrated DNA Technologies, Inc. , Coralville, Iowa.
3 Department of Clinical Genetics, Centre for Rare Diseases, Karolinska University Hospital , Stockholm, Sweden .
4 Department of Physiology, Anatomy and Genetics, University of Oxford , Oxford, United Kingdom .


New advances in oligonucleotide (ON) chemistry emerge continuously, and over the last few years, several aspects of ON delivery have been improved. However, clear knowledge regarding how certain chemistries behave alone, or in combination with various delivery vectors, is limited. Moreover, characterization is frequently limited to a single reporter cell line and, when different cell types are studied, experiments are commonly not carried out under similar conditions, hampering comparative analysis. To address this, we have developed a small "tissue" library of new, stable, pLuc/705 splice-switching reporter cell lines (named HuH7_705, U-2 OS_705, C2C12_705, and Neuro-2a_705). Our data show that, indeed, the cell type used in activity screenings influences the efficiency of ONs of different chemistry (phosphorothioate with locked nucleic acid or 2'-O-methyl with or without N,N-diethyl-4-(4-nitronaphthalen-1-ylazo)-phenylamine). Likewise, the delivery method, Lipofectamine® 2000, PepFect14 nanoparticles, or "naked" uptake, also demonstrates cell-type-dependent outcomes. Taken together, these cell lines can potentially become useful tools for future in vitro evaluation of new nucleic acid-based oligomers as well as delivery compounds for splice-switching approaches and cell-specific therapies.


delivery vectors; gymnotic delivery; oligonucleotide chemistries; pLuc 705; reporter cell lines; splice-switching oligonucleotides

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