In vivo delivery of transcription factors with multifunctional oligonucleotides Murthy Laboratory U.C. Berkeley Department of Bioengineering.

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In vivo delivery of transcription factors with multifunctional oligonucleotides Murthy Laboratory U.C. Berkeley Department of Bioengineering

Nrf2 plays a central role in protecting cells from oxidative stress

Galactose DART Nrf2 promoter sequence Endosomal disruption labile linkage Gal DNA Assembled Recombinant Transcription Factor Delivery (DARTs)

Hydrolyzed DART pH 5 in endosome Unmasked hydrophobic domain Nrf2 release in cytoplasm DART-Nrf2 Receptor mediated endocytosis DARTs are designed to deliver Nrf2

DARTs undergo pH sensitive hydrolysis

DARTs are pH sensitive membrane disruptive agents

DARTs can deliver Nrf2 to cells Nrf2DART-Nrf2

HO1 NQO1 GCLC GAPDH Control Free Nrf2DART-Nrf2 DARTs can deliver Nrf2 to hepatocytes and transcribe downstream genes

DARTs are designed to deliver Nrf2 and treat liver disease

APAP DARTs can deliver Nrf2 in vivo and rescue mice from drug induced liver toxicity

Infection Imaging Diagnosing infections at an early stage is a central challenge in medicine

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MDPs are robustly internalized by bacteria MDP-1 mM / CFU EC PA BS SA

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CuI, DIPEA, DMF, rt 1.K 18 F, CH 3 CN, 110 ⁰C; 2.NaOH, H 2 O, 110 ⁰C MH 18 F Maltohexaose- 18 F (MH 18 F) for PET imaging Angewandte Chemie International accepted for publication 2014

MH 18 F images bacteria by Micro- CT/PET 10 9 EC Control 10 9 CFUs ECControl *** Relative radio activity Angewandte Chemie International accepted for publication 2014

Conclusions Imaging Bacteria Transcription Factor Delivery Gal

Acknowledgments Funding from the NIH