Overview
Arrowhead has established a robust and versatile drug discovery and development platform based on proprietary technologies, broad licenses to fundamental intellectual property and extensive scientific expertise after more than a decade working on RNAi-based therapies. This platform enables the company to develop effective new therapies rapidly, cost effectively and potentially with lower risk relative to traditional approaches.
RNA Interference
One of the most important recent advances in biology, the discovery of RNA interference, or RNAi, led to a Nobel Prize in 2006. RNAi refers to a natural cellular mechanism whereby short oligonucleotide molecules called RNAi triggers silence gene expression and regulate the production of proteins. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing to target and shut down specific genes that cause disease. This mechanism offers many potential advantages in the development of disease therapies, including the ability to target a broad range of genes and proteins with high specificity, and also target disease pathways that have proven difficult to address with traditional small molecule and biologic therapeutics.
Read More »Targeted RNAi Molecule (TRiMTM) Platform
Arrowhead’s Targeted RNAi Molecule, or TRiMTM, platform utilizes ligand-mediated delivery and is designed to enable tissue-specific targeting while being structurally simple. Targeting has been core to Arrowhead’s development philosophy and the TRiMTM platform builds on more than a decade of work on actively targeted drug delivery vehicles. Arrowhead scientists have discovered ways to progressively “TRiM” away extraneous features and chemistries and retain optimal pharmacologic activity.
The TRiMTM platform comprises a highly potent RNA trigger with the following components optimized, as needed, for each drug candidate: a high affinity targeting ligand; various linker and chemistries; structures that enhance pharmacokinetics; and highly potent RNAi triggers with sequence specific stabilization chemistries.
Therapeutics developed with the TRiMTM platform offer several advantages: simplified manufacturing and reduced costs; multiple routes of administration; potential for improved safety because there are less metabolites from smaller molecules, thereby reducing the risk of intracellular buildup.
At Arrowhead, we also believe that for RNAi to reach its true potential, it must target organs outside the liver. Arrowhead is leading this expansion with the TRiMTM platform that holds the promise of reaching multiple tissues, including liver, lung, and tumor.
RNA Chemistries
The structure and chemistries of the oligonucleotide molecules used to trigger the RNAi mechanism can be tailored for optimal activity. Arrowhead’s broad portfolio of RNA trigger structures and chemistries, including some proprietary structures, enable the company to optimize each drug candidate on a target-by-target basis and utilize the combination of structure and chemical modifications that yield the most potent RNAi trigger.
As a component of the TRiM platform, Arrowhead’s design philosophy on RNA chemical modifications is to start with a structurally simple molecule and only add selective modification and stabilization chemistries as necessary to achieve the desired level of target knockdown and duration of effect. The conceptual framework for the stabilization strategy starts with a more sophisticated RNAi trigger screening and selection process that identifies potent sequences rapidly in locations that others may miss. We pursue chemical stabilization strategies with a target duration of effect of 30-90 days, and typically limit the use of strategies that produce longer activity because we anticipate that such strategies will increase long-term safety risks.
Intellectual Property
Our intellectual property portfolio provides broad freedom to apply multiple RNAi delivery technologies, chemistries, structures and manufacturing techniques in the development of novel therapeutics. Access to a broad range of technologies allows us to choose the best approach for a wide range of gene targets and disease indications.
Publications
2023
Gerald F. Watts, Christian Schwabe, Russell Scott, Patrick A. Gladding, David Sullivan, John Baker, Peter Clifton, James Hamilton, Bruce Given, Stacey Melquist, Rong Zhou, Ting Chang, Javier San Martin, Daniel Gaudet, Ira J. Goldberg, Joshua W. Knowles, Robert A. Hegele & Christie M. Ballantyne, RNA interference targeting ANGPTL3 for triglyceride and cholesterol lowering: phase 1 basket trial cohorts. 2023 Aug 25
Abstract: https://www.nature.com/articles/s41591-023-02494-2
Thomas N. Kakuda, PharmD1 , Atef Halabi, MD, PhD2, Gernot Klein, MD3, Madhu Sanga, PhD1, Carine Guinard-Azadian, MD4, Monika Kowalik, MD5, Katja Nedoschinsky4, Julius Nangosyah, MS4, Emmanuel Njumbe Ediage, PharmD4, Vera Hillewaert, MS4, Peter Verboven, BS4, Ivo Goris4, Jan Snoeys, PhD4, Martyn Palmer, MBA5, and Michael Biermer, MD4, Pharmacokinetics of JNJ-73763989 and JNJ-56136379 (Bersacapavir) in Participants With Moderate Hepatic Impairment, Clin Pharmacol. 2023 Feb 14
Abstract: https://pubmed.ncbi.nlm.nih.gov/36786053/
Haiyan Li, Xiaoye Niu, Yu Zhang, Danning Zhang, Yanqing Zhang, Liqun Wang, Yongqing Miao, Yanxin Jiang,Jia Ji, Qiaoqiao Chen, Xiaoyun Wu, Emmanuel Njumbe Ediage, Thomas N. Kakuda, and Michael Biermer, Pharmacokinetics, Safety, and Tolerability of the siRNA JNJ-73763989 in Healthy Chinese Adult Participants, Clinical Pharmacology in Drug Development 2023, 12(2) 175–180
Abstract: https://accp1.onlinelibrary.wiley.com/doi/abs/10.1002/cpdd.1197
Mak, Lung-Yi, Gane, E., Schwabe, C., Yoon, K., Heo, J., Scott, R., Lee, J., Kweon, Y., Weltman, M., Harrison, S., Neuschwander-Tetri, B., Cusi, K., Loomba, R., Given, B., Christianson, D., Garcia-Medel, E., Yi, M., Hamilton, J., Yuen, M., A phase I/II study of ARO-HSD, an RNA interference therapeutic, for the treatment of non-alcoholic steatohepatitis, Journal of Hepatology (2023), VOLUME 78, ISSUE 4, P684-692.
Full Text: https://www.journal-of-hepatology.eu/article/S0168-8278(22)03320-7/fulltext
2022
Ed Gane, Man-Fung Yuen, Thomas N Kakuda, Tetsuro Ogawa, Yasushi Takahashi, Nele Goeyvaerts, Isabelle Lonjon-Domanec, Tamisha Vaughan, Thomas Schluep, James Hamilton, Emmanuel Njumbe Ediage, Vera Hillewaert, Jan Snoeys, Oliver Lenz, Willem Talloen, Michael Biermer, JNJ-73763989 pharmacokinetics and safety: Liver-targeted siRNAs against hepatitis B virus, in Japanese and non-Japanese healthy adults, and combined with JNJ-56136379 and a nucleos(t)ide analogue in patients with chronic hepatitis B Antivir Ther. 2022 Jun;27(3)
Abstract: https://pubmed.ncbi.nlm.nih.gov/35695169/
Yuanqing Ma, Allison Joyce, Olivia Brandenburg, Faeze Saatchi, Christina Stevens, Vanina Toffessi Tcheuyap, Alana Christie, Quyen N. Do, Oluwatomilade Fatunde, Alyssa Macchiaroli, So C. Wong, Layton Woolford, Qurratulain Yousuf, Jeffrey Miyata, Deyssy Carrillo, Oreoluwa Onabolu, Tiffani McKenzie, Akhilesh Mishra, Tanner Hardy, Wei He, Daniel Li, Alexander Ivanishev, Qing Zhang, Ivan Pedrosa, Payal Kapur, Thomas Schluep, Steven B. Kanner, James Hamilton, and James Brugarolas, HIF2 Inactivation and Tumor Suppression with a Tumor-Directed RNA-Silencing Drug in Mice and Humans
Michael J. Koren, Patrick Maurice Moriarty, Seth J. Baum, Joel Neutel, Martha Hernandez-Illas, Howard S. Weintraub, Monica Florio, Helina Kassahun, Stacey Melquist, Tracy Varrieur, Saptarsi M. Haldar, Winnie Sohn, Huei Wang, Mary Elliott-Davey, Brooke M. Rock, Tao Pei, Oliver Homann, Jennifer Hellawell & Gerald F. Watts, Preclinical development and phase 1 trial of a novel siRNA targeting lipoprotein(a), Nature Medicine volume 28, 96-103 (2022)
Abstract: https://www.nature.com/articles/s41591-021-01634-w
Lung-Yi Mak, Ed Gane, Christian Schwabe, Ki Tae Yoon, Jeong Heo, Russell Scott, Jeong-Hoon Lee, Jung Il Lee, Young Oh Kweon, Martin Weltman, Stephen A. Harrison, Brent A. Neuschwander-Tetri, Kenneth Cusi, Rohit Loomba, Bruce D. Given, Dawn R. Christianson, Eric Garcia-Medel, Min Yi, James Hamilton, Man-Fung Yuen, A phase I/II study of ARO-HSD, an RNA interference therapeutic, for the treatment of non-alcoholic steatohepatitis, J Hepatol. 2023 Apr;78(4):684-692
Abstract: https://pubmed.ncbi.nlm.nih.gov/36513186/
Michelle L. O’Donoghue, MD, MPH, J. Antonio G. López, MD , Beat Knusel, PhD, Baris Gencer, MD, Huei Wang, PhD, You Wu, PhD b , Helina Kassahun, MD, and Marc S. Sabatine, MD, MPH, Study design and rationale for the Olpasiran trials of Cardiovascular Events And lipoproteiN(a) reduction-DOSE finding study (OCEAN(a)-DOSE), American Heart Journal, Volume 251, September 2022, Pages 61-69.
Abstract: https://www.sciencedirect.com/science/article/pii/S0002870322000862
Michelle L O’Donoghue, Robert S Rosenson, Baris Gencer, J Antonio G López, Norman E Lepor, Seth J Baum, Elmer Stout, Daniel Gaudet, Beat Knusel, Julia F Kuder, Xinhui Ran, Sabina A Murphy, Huei Wang, You Wu, Helina Kassahun, Marc S Sabatine; OCEAN(a)-DOSE Trial Investigators, Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease, N Engl J Med. 2022 Nov 17;387(20):1855-1864
Abstract: https://pubmed.ncbi.nlm.nih.gov/36342163/
Louis Sandra, Huybrecht T’jollyn, Nele Goeyvaerts, An Vermeulen, Anne-Ga€elle Dosne,
and Juan-Jose Perez-Ruixo, Plasma and Liver Pharmacokinetics of the N-Acetylgalactosamine Short Interfering RNA JNJ-73763989 in Recombinant Adeno-Associated–Hepatitis B Virus–Infected Mice, J Pharmacol Exp Ther. 2022 Oct;383(1):70-79
Abstract: https://pubmed.ncbi.nlm.nih.gov/36041884/
Winnie Sohn, PhD; Peter Winkle, MD; Joel Neutel, MD ; You Wu, PhD; Freeman Jabari; Caitlin Terrio, MSHS ; Tracy Varrieur, BSN ; Jingying Wang, PhD; and Jennifer Hellawell, MD, Pharmacokinetics, Pharmacodynamics, and Tolerability of Olpasiran in Healthy Japanese and Non-Japanese Participants: Results from a Phase I, Single-dose, Open-label Study, Clin Ther. 2022 Sep;44(9):1237-1247
Abstract: https://pubmed.ncbi.nlm.nih.gov/35963802/
Man-Fung Yuen, Danny Ka-Ho Wong, Thomas Schluep, Ching-Lung Lai, Carlo Ferrari, Stephen Locarnini, Regina Cheuk-Lam Lo, Robert G Gish, James Hamilton, Christine I Wooddell, Lung Yi Mak, Bruce D Given, Long-term serological, virological and histological responses to RNA inhibition by ARC-520 in Chinese chronic hepatitis B patients on entecavir treatment, Gut. 2022 Apr;71(4):789-797.
Abstract: https://pubmed.ncbi.nlm.nih.gov/33712437/
Man-Fung Yuen, Stephen Locarnini, Tien Huey Lim, Simone I Strasser, William Sievert, Wendy Cheng, Alex J Thompson, Bruce D Given, Thomas Schluep, James Hamilton, Michael Biermer, Ronald Kalmeijer, Maria Beumont, Oliver Lenz, Filip De Ridder, Gavin Cloherty, Danny Ka-Ho Wong, Christian Schwabe, Kathy Jackson, Ching Lung Lai, Robert G Gish, Edward Gane, Combination treatments including the small-interfering RNA JNJ-3989 induce rapid and sometimes prolonged viral responses in patients with CHB, J Hepatol. 2022 Nov;77(5):1287-1298
Abstract: https://pubmed.ncbi.nlm.nih.gov/35870702/
Pavel Strnad, M.D., Mattias Mandorfer, M.D., Ph.D., Gourab Choudhury, M.D., William Griffiths, M.D., Christian Trautwein, M.D., Rohit Loomba, M.D., Thomas Schluep, Sc.D., Ting Chang, Ph.D., Min Yi, Ph.D., Bruce D. Given, M.D., James C. Hamilton, M.D., Javier San Martin, M.D., et al., Fazirsiran for Liver Disease Associated with Alpha1-Antitrypsin Deficiency, N Engl J Med 2022; 387:514-524
Abstract: https://www.nejm.org/doi/full/10.1056/NEJMoa2205416
2021
Christine I. Wooddell, , Adam J. Gehring, Man-Fung Yuen and Bruce D. Given, RNA Interference Therapy for Chronic Hepatitis B Predicts the Importance of Addressing Viral Integration When Developing Novel Cure Strategies, Viruses. 2021 Mar 30;13(4):581
Abstract: https://pubmed.ncbi.nlm.nih.gov/33808298/
2020
Andrew A Butler, James L Graham, Kimber L Stanhope, So Wong, Sarah King, Andrew A Bremer, Ronald M Krauss, James Hamilton, Peter J Havel, Role of angiopoietin-like protein 3 in sugar-induced dyslipidemia in rhesus macaques: suppression by fish oil or RNAi, J Lipid Res. 2020 Mar;61(3):376-386.
Abstract: https://pubmed.ncbi.nlm.nih.gov/31919051/
Christine I. Wooddell, Keith Blomenkamp, Ryan M. Peterson, Vladimir M. Subbotin, Christian Schwabe, James Hamilton, Qili Chu, Dawn R. Christianson, Julia O. Hegge, John Kolbe, Holly L. Hamilton, Maria F. Branca-Afrazi, Bruce D. Given, David L. Lewis, Edward Gane, Steven B. Kanner, and Jeffrey H. Teckman, Development of an RNAi therapeutic for alpha-1-antitrypsin liver disease, JCI Insight. 2020 Jun 18;5(12):e135348
Abstract: https://pubmed.ncbi.nlm.nih.gov/32379724/
Man-Fung Yuen, Ingolf Schiefke, Jung-Hwan Yoon, Sang Hoon Ahn, Jeong Heo, Ju Hyun Kim, Henry Lik Yuen Chan, Ki Tae Yoon, Hartwig Klinker, Michael Manns, Joerg Petersen, Thomas Schluep, James Hamilton, Bruce D Given, Carlo Ferrari, Ching-Lung Lai, Stephen A Locarnini, Robert G Gish, RNA Interference Therapy With ARC-520 Results in Prolonged Hepatitis B Surface Antigen Response in Patients With Chronic Hepatitis B Infection, Hepatology. 2020 Jul;72(1):19-31
Abstract: https://pubmed.ncbi.nlm.nih.gov/31654573/
2019
Andrew A Butler, Candice A Price, James L Graham, Kimber L Stanhope, Sarah King, Yu-Han Hung, Praveen Sethupathy, So Wong, James Hamilton, Ronald M Krauss, Andrew A Bremer, Peter J Havel, Fructose-induced hypertriglyceridemia in rhesus macaques is attenuated with fish oil or ApoC3 RNA interference, J Lipid Res. 2019 Apr;60(4):805-818
Abstract: https://pubmed.ncbi.nlm.nih.gov/30723097/
2018
Alice M Turner, Jan Stolk, Robert Bals, Jason D Lickliter, James Hamilton, Dawn R Christianson, Bruce D Given, Jonathan G Burdon, Rohit Loomba, James K Stoller, Jeffery H Teckman, Hepatic-targeted RNA interference provides robust and persistent knockdown of alpha-1 antitrypsin levels in ZZ patients, J Hepatol. 2018 Aug;69(2):378-384
Abstract: https://pubmed.ncbi.nlm.nih.gov/29572094/
So C. Wong; Weijun Cheng; Holly Hamilton; Anthony L. Nicholas; Darren H. Wakefield; Aaron Almeida; Andrei V. Blokhin; Jeffrey Carlson; Zane C. Neal; Vladimir Subbotin; Guofeng Zhang; Julia Hegge; Stephanie Bertin; Vladimir S. Trubetskoy; David B. Rozema; David L. Lewis; Steven B. Kanner, HIF2α-Targeted RNAi Therapeutic Inhibits Clear Cell Renal Cell Carcinoma, Mol Cancer Ther (2018) 17 (1): 140–149
2017
Wooddell CI, Yuen MF, Chan HL, Gish RG, Locarnini SA, Chavez D, Ferrari C, Given BD, Hamilton J, Kanner SB, Lai CL, Lau JYN, Schluep T, Xu Z, Lanford RE, and Lewis DL, RNAi-based treatment of chronically infected patients and chimpanzees reveals that integrated hepatitis B virus DNA is a source of HBsAg. Science Translational Medicine (2017 Sep 27), 9(409), eaan0241.
2015
Sebestyén MG, Wong SC, Trubetskoy V, Lewis DL, Wooddell CI (2015) “Targeted in vivo delivery of siRNA and an endosome-releasing agent to hepatocytes.” Chapter in RNA Interference: Challenges and Therapeutic Opportunities, Mouldy Sioud (ed.), Methods in Molecular Biology vol. 1218.
Gish RG, Yuen MF, Chan HLY, Given BD, Lai CL, Locarnini SA, Lau JYN, Wooddell CI, Schluep T, Lewis DL (2015) “Synthetic RNAi triggers and their use in chronic hepatitis B therapies with curative intent.” Antiviral Research 2015 Sep;121:97-108.
Gish RG, Given BD, Lai CL, Locarnini SA, Lau JY, Lewis DL, Schluep T. (2015) “Chronic hepatitis B: Virology, natural history, current management and a glimpse at future opportunities.” Antiviral Research 2015 Sep;121:47-58.
Rozema DB, Blokhin AV, Wakefield DH, Benson JD, Carlson JC, Klein JJ, Almeida LJ, Nicholas AL, Hamilton HL, Chu Q, Hegge JO, Wong SC, Trubetskoy VS, Hagen CM, Kitas E, Wolff JA, Lewis DL. “Protease-triggered siRNA delivery vehicles.” Journal of Controlled Release. 14 April 2015; doi:10.1016/j.jconrel.2015.04.012.
2013
Wooddell CI, Rozema DB, Hossbach M, John M, Hamilton HL, Chu Q, Hegge JO, Klein JJ, Wakefield DH, Oropeza CE, Deckert J, Roehl I, Jahn-Hofmann K, Hadwiger P, Vornlocher HP, McLachlan A, Lewis DL, “Hepatocyte-targeted RNAi Therapeutics for the Treatment of Chronic Hepatitis B Virus Infection.” Molecular Therapy. 26 February 2013; doi: 10.1038/mt.2013.31.
2012
Schneider B, Grote M, John M, Haas A, Bramlage B, Ickenstein LM, Jahn-Hofmann K, Bauss F, Cheng W, Croasdale R, Daub K, Dill S, Hoffmann E, Lau W, Burtscher H, Ludtke JL, Metz S, Mundigl O, Neal ZC, Scheuer W, Stracke J, Herweijer H, Brinkmann U. “Targeted siRNA Delivery and mRNA Knockdown Mediated by Bispecific Digoxigenin-binding Antibodies.” Molecular Therapy Nucleic Acids. 18 September 2012; 1, e45; doi:10.1038/mtna.2012.39
Wong SC, Klein JJ, Hamilton HL, Chu Q, Frey CL, Trubetskoy VS, Hegge J, Wakefield D, Rozema DB, Lewis DL. “Co-Injection of a Targeted, Reversibly Masked Endosomolytic Polymer Dramatically Improves the Efficacy of Cholesterol-Conjugated Small Interfering RNAs In Vivo.” Nucleic Acid Therapeutics. December 2012; 22(6): 380-390. doi:10.1089/nat.2012.0389.
2011
Wooddell CI, Hegge JO, Zhang G, Sebestyén MG, Noble M, Griffin JB, Pfannes LV, Herweijer H, Hagstrom JE, Braun S, Huss T, Wolff JA “Dose response in rodents and nonhuman primates after hydrodynamic limb vein delivery of naked plasmid DNA”. Human Gene Therapy 2011 July; 22(7):889-903. doi: 10.1089/hum.2010.160. Epub 2011 Apr 18.
Wooddell CI, Subbotin VM, Sebestyén MG, Griffin JB, Zhang G, Schleef M, Braun S, Huss T, Wolff JA “Muscle damage after delivery of naked plasmid DNA into skeletal muscles is batch dependent”. Human Gene Therapy February 2011; 22:225-235. DOI: 10.1089/hum.2010.113
Wooddell CI, Radley-Crabb HG, Griffin JB, Zhang G “Myofiber damage evaluation by evans blue dye injection”. Current Protocols in Mouse Biology 1: 1-26, December 2011. DOI: 10.1002/9780470942390.mo110141
Pichavant C, Aartsma-Rus A, Clemens PR, Davies KE, Dickson G, Takeda S, Wilton SD, Wolff JA, Wooddell CI, Xiao X, Tremblay JP “Current status of pharmaceutical and genetic therapeutic approaches to treat DMD”. Molecular Therapy 2011 May; 19(5): 830–840. doi:10.1038/mt.2011.59
2010
Zhang G, Wooddell CI, Hegge JO, Griffin JB, Huss T, Braun S, Wolff JA “Functional efficacy of dystrophin expression from plasmids delivered to mdx mice by hydrodynamic limb vein injection”. Human Gene Therapy February 2010; 21:221-237. DOI: 10.1089/hum.2009.133
Wooddell CI, Zhang G, Griffin JB, Hegge JO, Huss T, Wolff JA “Use of evans blue dye to compare limb muscles in exercised young and old mdx mice”. Muscle and Nerve, April 2010. DOI 10.1002/mus.21527
Hegge JO, Wooddell CI, Zhang G, Hagstrom JE, Braun S, Huss T, Sebestyén MG, Emborg ME, Wolff JA “Evaluation of hydrodynamic limb vein injections in nonhuman primates”. Human Gene Therapy July 2010; 21:829-842. DOI: 10.1089/hum.2009.172
Mudd SR, Trubetskoy VS, Blokhin AV, Weichert JP, Wolff JA “Hybrid PET/CT for noninvasive pharmacokinetic evaluation of dynamic PolyConjugates, a synthetic siRNA delivery system.” Bioconjug Chem. 2010 Jul 21;21(7):1183-9. doi: 10.1021/bc900558z.
2007
Vigen KK, Hegge JO, Zhang G, Mukherjee R, Braun S, Grist TM, Wolff JA “Magnetic resonance imaging-monitored plasmid DNA delivery in primate limb muscle”.Human Gene Therapy March 2007; 18:257-268. DOI: 10.1089/hum.2006.115
Lewis, D. L., Wolff, J. A. (2007) “Systemic siRNA delivery via hydrodynamic intravascular injection.” Advanced Drug Delivery Reviews, 59, 115-123.
Sebestyen, M. G., Hegge, J. O., Noble, M. A., Lewis, D. L., Herweijer, H.,Wolff, J. A. (2007) “Progress toward a nonviral gene therapy protocol for the treatment of anemia.” Human Gene Therapy, 18, 269-85.
Dai, X., De Souza, A.T., Dai, H., Lewis, D. L., Lee, C., Spencer, A. G., Herweijer, H., Hagstrom, J. E., Linsley, P. S., Bassett, D. E., Ulrich, R. G., He, Y. D. (2007) “PPARα siRNA–Treated Expression Profiles Uncover the Causal Sufficiency Network for Compound-Induced Liver Hypertrophy.” PLoS Computational Biology, 3 (3).
Rozema DB, Lewis DL, Wakefield DH, Wong SC, Klein JJ, Roesch PL, Bertin SL, Reppen TW, Chu Q, Blokhin AV, Hagstrom JE, Wolff JA. “Dynamic PolyConjugates for targeted in vivo delivery of siRNA to hepatocytes.” Proceedings of the National Academy of Sciences. 104(32): 12982-87.
2006
De Souza, A. T., Dai, X., Spencer, A. G., Reppen, T., Menzie, A., Roesch, P. L., He, Y., Caguyong, M. J., Bloomer, S., Herweijer, H., Wolff, J. A., Hagstrom, J. E., Lewis, D. L., Linsley, P. S., Ulrich, R. G. (2006) “Transcriptional and phenotypic comparisons of Ppara knockout and siRNA knockdown mice.” Nucleic Acids Research, 34, 4486-4494.
Wong S. C., Wakefield D., Klein J., Monahan S. D., Rozema D. B., Lewis D. L., Higgs L., Ludtke J., Sokoloff A. V., Wolff J. A. (2006) “Hepatocyte Targeting of Nucleic Acid Complexes and Liposomes by a T7 Phage p17 Peptide.” Molecular Pharmacology, 3, 386-397.
Sebestyen, M. G., Budker, V. G., Budker, T., Subbotin, V. M., Zhang, G., Monahan, S. D., Lewis, D. L., Wong, S. C., Hagstrom, J. E., Wolff, J.A. (2006) “Mechanism of plasmid delivery by hydrodynamic tail vein injection. I. Hepatocyte uptake of various molecules.” Journal of Gene Medicine, 8, 852-873.
2005
Lewis, D. L. and Wolff, J. A. (2005) “Delivery of siRNA and siRNA Expression Constructs to Adult Mammals Using Hydrodynamic Intravascular Injection.” In Methods in Enzymology, 392, RNA Interference, Engelke, D. R. and Rossi, J. (Eds.). Elsevier/Academic Press, San Diego, CA.
Wolff, J., Lewis, D. L., Herweijer, H., Hegge, J., Hagstrom, J. (2005) “Non-viral approaches for gene transfer.” Acta Myol., 24, 202-8.
Wooddell, C. I., Van Hout, C. V., Reppen, T., Lewis, D. L., Herweijer, H. (2005) “Long-term RNA interference from optimized siRNA expression constructs in adult mice. Biochemical and Biophysical Research Communications,” 334, 117–127.
2004
Hagstrom, J. E., Hegge, J., Zhang, G., Noble, M., Budker, V., Lewis, D. L., Herweijer, H., and Wolff, J. A. (2004) “A facile method for delivering genes and siRNAs to skeletal muscle of mammalian limbs.” Molecular Therapy, 10, 386-398.
2003
Rozema, D. B., and Lewis, D. L., (2003) “siRNA delivery technologies for mammalian systems.” Targets, 2, 253-260.
Rozema, D. B., Ekena, K., Lewis, D. L., Loomis, A. G., and Wolff, J. A. (2003) “Endosomolysis by masking of a membrane-active agent (EMMA) for cytoplasmic release of macromolecules.” Bioconjugate Chemistry, 14, 51-57.
2002
Lewis, D. L., Hagstrom, J. E., Loomis, A. G., Wolff, J. A. and Herweijer, H. (2002) “Efficient delivery of siRNA for inhibition of gene expression in postnatal mice.” Nature Genetics 32, 107-108.