COVID-19 research support
The COVID-19 pandemic requires a global response, and Horizon is committed to supporting the fight against the novel coronavirus in any way possible. We currently have the capacity to meet and deliver order needs without delay. If your lab is in need of RNA reagents, please contact us immediately. See how COVID-19 is affecting Horizon's business operations here.
We are actively coordinating with labs working on COVID-19 research and detection, and are supporting this vital research in the following ways:
SARS-CoV-2 research tools
Study the function of human genes involved in cellular entry and host-pathogen interaction
- siRNA guaranteed to silence the target gene Single genes | libraries
- CRISPR activation for endogenous gene over-expression Single genes | libraries
- CRISPR knockout for guaranteed gene editing Single genes | libraries
- Knockout cell models in clinically relevant cell lines Ready-to-go lines | Custom engineering service
- Functional genomic screening services by our team of dedicated experts Gene knockout, knockdown and activation screens available in highly relevant cell types (e.g. A549s)
- Bioinformatic design tools, and reagents for genome engineering Use the HDR Donor Designer tool to generate guide RNAs and donor templates to investigate binding domain function, protein-protein interactions, study localization, etc.
Investigate viral gene function
- siRNA specifically designed to both silence viral genes, and minimize off-target repression of human genes
SARS-CoV-2 diagnostic tools
Ensure confidence in RT-PCR results with custom RNA controls by Dharmacon
- RNA controls - Run a Spike-in RNA control, or an RNA control alongside clinical samples to:
- Confirm that your diagnostic assay is working by verifying that it can amplify the RNA or DNA region of interest in each run
- Monitor the performance of your PCR mastermix
- Identify assay inhibition
- Primers for viral detection
ACE2 related research tools
Literature from the 2004 SARS outbreak, as well as current SARS-CoV-2 studies, point to the importance of ACE2, or angiotensin-converting enzyme-2 for viral entry into cells. ACE2 is the cellular receptor for both of these pandemic coronaviruses, as described in this recent paper in Science. The viral spike glycoprotein (S protein) interacts with a dimer of ACE2, complexed with a dimer of B0AT1. The molecular association is a crucial step in gating the SARS coronavirus entry into cells. Downstream, additional recent work implicates the transmembrane protease, serine 2 (TMPRSS2), as essential for S protein priming, with TMPRSS2 inhibition showing potential treatment options.
Horizon Discovery offers a full complement of siRNA, shRNA, CRISPR guide RNA, and knockout cell models for ACE2, B0AT1, and TMPRSS2 to help study these therapeutically relevant interactions between the virus and the host.
- ACE2 angiotensin I converting enzyme 2 (ACEH)
- SLC6A19 (B0AT1)
- TMPRSS2 transmembrane protease, serine 2 (PP9284)
Supporting viral research
Horizon (including the Dharmacon brand of siRNA, shRNA, miRNA and custom RNA reagents and libraries) has long been a pioneer in the study of host-pathogen interactions and cellular mechanisms involved in the transmission and progression of infectious diseases. Whole genome siRNA screens have discovered mechanisms in Trypanosoma cruzi infection (Genovesio, 2011), West Nile disease (Krishnan, 2008), influenza (Meliopoulos, 2012), and others.
Focused libraries (for instance targeting cellular membrane trafficking and kinases) have shed light on shared viral processes among HIV and related retroviruses (Wen 2014) and have discovered novel kinases involved in mumps virus replication (Briggs, 2020). Large siRNA screens have also been used to elucidate and improve mechanisms for vaccine production, for instance to combat rotavirus (Wu, 2017).
In addition, screens modulating miRNA activity have shed light on host factors which affect viral infection in a broad manner (McCaskill, 2017). A powerful addition to the screening arsenal includes CRISPR screening with arrayed Dharmacon sgRNAs in an investigation of T cell behavior in HIV infection (Hultquist, 2016). CRISPR screens for infectious disease elucidation can extend beyond gene knockout to include transcriptional gene regulation with CRISPRa and CRISPRi (Strich, 2019).
We would like to be your partner in screening projects, custom CRISPR-based cell line engineering, CRISPR or RNAi reagents, or anything else you can envision to help understand and combat this devastating disease. We are all in this together!
Briggs K, Wang L, Nagashima K, Zengel J, Tripp RA, He B. Regulation of Mumps Virus Replication and transcription by kinase RPS6KB1. JVI accepted manuscript, posted online Apr 15, 2020.Genovesio A, Giardini MA, Kwon YJ, de Macedo Dossin F, Choi SY, Kim NY, Kim HC, Jung SY, Schenkman S, Almeida IC, Emans N, Freitas-Junior LH. Visual genome-wide RNAi screening to identify human host factors required for Trypanosoma cruzi infection. PLoS One. 2011;6(5):e19733.Hultquist JF, Schumann K, Woo JM, Manganaro L, McGregor MJ, Doudna J, Simon V, Krogan NJ, Marson A. A Cas9 Ribonucleoprotein Platform for Functional Genetic Studies of HIV-Host Interactions in Primary Human T Cells. Cell Rep. 2016 Oct 25;17(5):1438-1452.Krishnan MN, Ng A, Sukumaran B, Gilfoy FD, Uchil PD, Sultana H, Brass AL, Adametz R, Tsui M, Qian F, Montgomery RR, Lev S, Mason PW, Koski RA, Elledge SJ, Xavier RJ, Agaisse H, Fikrig E. RNA interference screen for human genes associated with West Nile virus infection. Nature. 2008 Sep 11;455(7210):242-5. doi: 10.1038/nature07207.McCaskill JL, Ressel S, Alber A, Redford J, Power UF, Schwarze J, Dutia BM, Buck AH. Broad-Spectrum Inhibition of Respiratory Virus Infection by MicroRNA Mimics Targeting p38 MAPK Signaling. Mol Ther Nucleic Acids. 2017 Jun 16;7:256-266.Meliopoulos VA, Andersen LE, Birrer KF, Simpson KJ, Lowenthal JW, Bean AG, Stambas J, Stewart CR, Tompkins SM, van Beusechem VW, Fraser I, Mhlanga M, Barichievy S, Smith Q, Leake D, Karpilow J, Buck A, Jona G, Tripp RA. Host gene targets for novel influenza therapies elucidated by high-throughput RNA interference screens. FASEB J. 2012 Apr;26(4):1372-86.Strich JR, Chertow DS. CRISPR-Cas Biology and Its Application to Infectious Diseases. J Clin Microbiol. 2019 Mar 28;57(4).
Wen X, Ding L, Hunter E, Spearman P. An siRNA screen of membrane trafficking genes highlights pathways common to HIV-1 and M-PMV virus assembly and release. PLoS One. 2014 Sep 4;9(9):e106151.
Wu W, Orr-Burks N, Karpilow J, Tripp RA. Development of improved vaccine cell lines against rotavirus. Sci Data. 2017 Mar 1;4:170021.