The mission of CELLSCRIPT™is to provide the best products and technologies for making andusing RNA for translation in cells for clinical research and therapeutics.

Current products include kits for in vitro transcription,5 RNA capping using either a cap analog or capping enzymes, and3 RNA polyadenylation, as well as all-in-one kits for making capped,poly(A)-tailed mRNA for translation in cells.

CELLSCRIPT™recently introduced INCOGNITO™ RNA Transcription Kitsfor in vitro synthesis of RNA that contains modified nucleosides,such as pseudouridine (Ψ) and/or 5-methylcytidine (m5C) in place ofthe corresponding U or C canonical nucleosides (Figure 1). These kitsare so-named because the capped, polyadenylated and nucleoside-modifiedRNA products (called INCOGNITO mRNAs ) are disguised sothey do not induce innateimmune responses to the same extent as the corresponding unmodifiedmRNAs when transfected into mammalian cells that express a variety ofRNA sensors.

As documented in journal articles1–3 and patent applications,4the technologies on which INCOGNITO RNA kits and other products arebased were invented by Professors Katalin Karikó and Drew Weissman atthe University of Pennsylvania and exclusively licensed to CELLSCRIPT™for all fields of use. Drs. Weissman and Karikó showed that INCOGNITOmRNA, besides being less immunogenic, is translated into protein atmuch higher levels than the corresponding mRNA that does not containmodified nucleosides, both in cultured cells (Figure 2) and in wholeorganisms (Figure 3). INCOGNITO-type Ψ- and m5C-modified mRNA encodingKLF4, LIN28, cMYC, OCT4 and SOX2 that was repeatedly transfected intosomatic cells, such as fibroblasts and keratinocytes, resulted in highlyefficient generation of induced pluripotent stem cells.5

The delivery of protein-encoding INCOGNITO mRNA to cells in cultureor in vivo to an organism has the potential to produce a therapeuticeffect by compensating for a missing or defective protein, overexpressinga desired protein, inducing a change in cellular phenotype, or triggeringa disease-specific immune response. Thus, we believe INCOGNITO mRNAswill have many uses in regenerative medicine, such as for: cellreprogramming; cell therapies; cell, tissue or organ transplantationor repair; tissue or organ engineering; enzyme replacementtherapies; and immunotherapies or immunomodulation therapies.

Contact CELLSCRIPT™to discuss kits for making research or therapeutic grades of INCOGNITOmRNA or unmodified RNA, or possible custom manufacturing of an appropriategrade and scale of RNA for your project.

References Karikó K, Buckstein M, Ni H, Weissman D. Immunity 23: 165–75, 2005. Suppression of RNA recognitionby Toll-like receptors: The impact of nucleoside modification andthe evolutionary origin of RNA.Journal Article Karikó K, Muramatsu H, Welsh FA, Ludwig J, Kato H, Akira S,Weissman D. Molecular Therapy 16: 1833–40,2008. Incorporation of pseudouridine into mRNA yields superior nonimmunogenicvector with increased translational capacity and biological stability.Journal Article Anderson B. Muramatsu H, Nallagatla SR, Bevilacqua P. SansingL, Weissman D, Karikó K. Nucleic Acids Res 38:5884–92, 2010. Incorporation of pseudouridine into mRNA enhancestranslation by diminishing PKR activation.Journal Article E.g., United States Patent Application No. US 20090286852Journal Article Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, Ebina W,Mandal PK, Smith ZD, Meissner A, Daley GQ, Brack AS, Collins JJ,Cowan C, Schlaeger TM, Rossi DJ. Cell Stem Cell. 7(5): 549–50, 2010. Journal Article