Dr. Ryan P. Bennett

The People of OyaGen

Dr. Ryan P. Bennett, Chief Scientific Officer and Laboratory Director

Dr. Ryan Bennett
Dr. Ryan P. Bennett

The Chief Scientific Officer (CSO) and Lab Director at OyaGen Dr. Ryan Bennett has been a leader in assay development for high throughput screening (HTS), downstream target validation and late stage preclinical drug development. Both his graduate and professional research experience has been focused on viral host defense enabling him to develop novel HTS assays for screening new HIV/AIDS and Ebola therapeutics. This experience has given him extensive background knowledge on HTS, and preclinical development for viral infections and host defense.Ryan also has extensive experience developing assays for elucidating mechanism of action (MOA) for drug targets. Since becoming Lab Manager in 2009 he has had multiple senior scientists and technicians under his direct supervision and has overseen the development and execution of the multiple primary screens against OyaGen’s in-house ~25K compound library, the NCI open repository library and one primary screen against a 110K compound library transferred to OyaGen from Sanford Burnham Prebys along with secondary screens and functional endpoint analyses. With his promotion to CSO in 2014 and in his continued role as Lab Director he manages the day-to-day operations of all projects and staff within OyaGen along with our contract research organizations (CROs) for developing assays on targets in the anti-HIV Vif and A3G pathway as well as targets for Ebola and SARS-CoV-2. In his 15+ years at OyaGen he has gained extensive assay development experience constructing and optimizing various primary, secondary and counter screens to validate multiple lead compounds in hit-to-lead development. These activities have enabled him to lead the interactions with CROs for HTS of 100K to 300K compound libraries along with downstream viral and toxicity tests. In his leadership role for preclinical development, he coordinates third party CROs in next gen sequencing, medicinal chemistry, live virus studies, ADMET, PK and animal efficacy testing for lead-to-candidate development towards IND-enabling studies for the FDA. He has served as point person in our research agreements with scientists from government and pharma partners. He also is responsible for analyzing and organizing data for presentations at scientific meetings, for manuscripts and for investors.


Bennett RP, Postnikova EN, Eaton BP, Cai Y, Yu S, Smith CO, Liang J, Zhou H, Kocher GA, Murphy MJ, Smith HC, Kuhn JH. Sangivamycin is highly effective against SARS-CoV-2 in vitro and has favorable drug properties. JCI Insight2022 Jan 11;7(1)doi: 10.1172/jci.insight.153165. PubMed PMID: 34807849; PubMed Central PMCID: PMC8765048.
Bennett RP, Finch CL, Postnikova EN, Stewart RA, Cai Y, Yu S, Liang J, Dyall J, Salter JD, Smith HC, Kuhn JH. A Novel Ebola Virus VP40 Matrix Protein-Based Screening for Identification of Novel Candidate Medical Countermeasures. Viruses2020 Dec 31;13(1)doi: 10.3390/v13010052. PubMed PMID: 33396288; PubMed Central PMCID: PMC7824103.
Salter JD, Polevoda B, Bennett RP, Smith HC. Regulation of Antiviral Innate Immunity Through APOBEC Ribonucleoprotein Complexes. Subcell Biochem2019;93:193-219doi: 10.1007/978-3-030-28151-9_6. Review. PubMed PMID: 31939152.
Bennett RP, Salter JD, Smith HC. A New Class of Antiretroviral Enabling Innate Immunity by Protecting APOBEC3 from HIV Vif-Dependent Degradation. Trends Mol Med2018 May;24(5):507-520doi: 10.1016/j.molmed.2018.03.004. Epub 2018 Mar 30. Review. PubMed PMID: 29609878; PubMed Central PMCID: PMC7362305.
Hilimire TA, Chamberlain JM, Anokhina V, Bennett RP, Swart O, Myers JR, Ashton JM, Stewart RA, Featherston AL, Gates K, Helms ED, Smith HC, Dewhurst S, Miller BL. HIV-1 Frameshift RNA-Targeted Triazoles Inhibit Propagation of Replication-Competent and Multi-Drug-Resistant HIV in Human Cells. ACS Chem Biol2017 Jun 16;12(6):1674-1682doi: 10.1021/acschembio.7b00052. Epub 2017 May 5. PubMed PMID: 28448121; PubMed Central PMCID: PMC5477779.
Polevoda B, Joseph R, Friedman AE, Bennett RP, Greiner R, De Zoysa T, Stewart RA, Smith HC. DNA mutagenic activity and capacity for HIV-1 restriction of the cytidine deaminase APOBEC3G depend on whether DNA or RNA binds to tyrosine 315. J Biol Chem2017 May 26;292(21):8642-8656doi: 10.1074/jbc.M116.767889. Epub 2017 Apr 5. PubMed PMID: 28381554; PubMed Central PMCID: PMC5448093.
Bennett RP, Stewart RA, Hogan PA, Ptak RG, Mankowski MK, Hartman TL, Buckheit RW Jr, Snyder BA, Salter JD, Morales GA, Smith HC. An analog of camptothecin inactive against Topoisomerase I is broadly neutralizing of HIV-1 through inhibition of Vif-dependent APOBEC3G degradation. Antiviral Res2016 Dec;136:51-59doi: 10.1016/j.antiviral.2016.11.001. Epub 2016 Nov 5. PubMed PMID: 27825797; PubMed Central PMCID: PMC5125868.
Polevoda B, McDougall WM, Bennett RP, Salter JD, Smith HC. Structural and functional assessment of APOBEC3G macromolecular complexes. Methods2016 Sep 1;107:10-22doi: 10.1016/j.ymeth.2016.03.006. Epub 2016 Mar 14. PubMed PMID: 26988126; PubMed Central PMCID: PMC5014647.
Salter JD, Bennett RP, Smith HC. The APOBEC Protein Family: United by Structure, Divergent in Function. Trends Biochem Sci2016 Jul;41(7):578-594doi: 10.1016/j.tibs.2016.05.001. Epub 2016 Jun 6. Review. PubMed PMID: 27283515; PubMed Central PMCID: PMC4930407.
Hilimire TA, Bennett RP, Stewart RA, Garcia-Miranda P, Blume A, Becker J, Sherer N, Helms ED, Butcher SE, Smith HC, Miller BL. N-Methylation as a Strategy for Enhancing the Affinity and Selectivity of RNA-binding Peptides: Application to the HIV-1 Frameshift-Stimulating RNA. ACS Chem Biol2016 Jan 15;11(1):88-94doi: 10.1021/acschembio.5b00682. Epub 2015 Nov 3. PubMed PMID: 26496521; PubMed Central PMCID: PMC4720131.
Prohaska KM, Bennett RP, Salter JD, Smith HC. The multifaceted roles of RNA binding in APOBEC cytidine deaminase functions. Wiley Interdiscip Rev RNA2014 Jul-Aug;5(4):493-508doi: 10.1002/wrna.1226. Epub 2014 Mar 24. Review. PubMed PMID: 24664896; PubMed Central PMCID: PMC4062598.
Ofori LO, Hilimire TA, Bennett RP, Brown NW Jr, Smith HC, Miller BL. High-affinity recognition of HIV-1 frameshift-stimulating RNA alters frameshifting in vitro and interferes with HIV-1 infectivity. J Med Chem2014 Feb 13;57(3):723-32doi: 10.1021/jm401438g. Epub 2014 Jan 15. PubMed PMID: 24387306; PubMed Central PMCID: PMC3954503.
Smith HC, Bennett RP, Kizilyer A, McDougall WM, Prohaska KM. Functions and regulation of the APOBEC family of proteins. Semin Cell Dev Biol2012 May;23(3):258-68doi: 10.1016/j.semcdb.2011.10.004. Epub 2011 Oct 6. Review. PubMed PMID: 22001110; PubMed Central PMCID: PMC4017262.
Bennett RP, Salter JD, Liu X, Wedekind JE, Smith HC. APOBEC3G subunits self-associate via the C-terminal deaminase domain. J Biol Chem2008 Nov 28;283(48):33329-36doi: 10.1074/jbc.M803726200. Epub 2008 Oct 8. PubMed PMID: 18842592; PubMed Central PMCID: PMC2586250.
Bennett RP, Presnyak V, Wedekind JE, Smith HC. Nuclear Exclusion of the HIV-1 host defense factor APOBEC3G requires a novel cytoplasmic retention signal and is not dependent on RNA binding. J Biol Chem2008 Mar 21;283(12):7320-7doi: 10.1074/jbc.M708567200. Epub 2007 Dec 28. PubMed PMID: 18165230.
Wedekind JE, Gillilan R, Janda A, Krucinska J, Salter JD, Bennett RP, Raina J, Smith HC. Nanostructures of APOBEC3G support a hierarchical assembly model of high molecular mass ribonucleoprotein particles from dimeric subunits. J Biol Chem2006 Dec 15;281(50):38122-6doi: 10.1074/jbc.C600253200. Epub 2006 Oct 31. PubMed PMID: 17079235; PubMed Central PMCID: PMC1847398.
Bennett RP, Diner E, Sowden MP, Lees JA, Wedekind JE, Smith HC. APOBEC-1 and AID are nucleo-cytoplasmic trafficking proteins but APOBEC3G cannot traffic. Biochem Biophys Res Commun2006 Nov 10;350(1):214-9doi: 10.1016/j.bbrc.2006.09.032. Epub 2006 Sep 18. PubMed PMID: 16999936; PubMed Central PMCID: PMC1847397.
Tomari Y, Du T, Haley B, Schwarz DS, Bennett R, Cook HA, Koppetsch BS, Theurkauf WE, Zamore PD. RISC assembly defects in the Drosophila RNAi mutant armitage. Cell2004 Mar 19;116(6):831-41doi: 10.1016/s0092-8674(04)00218-1. PubMed PMID: 15035985.