Press releases

Sept. 18, 2018, 3:38 p.m.
National Institute of Health awards Mirimus with SBIR Grant- High efficiency platform for rapid RNAi rat model development
Rats have long served as valuable preclinical tools to evaluate toxicity of novel compounds before they enter clinical trials. With this NIH SBIR award (ORIP: 1 R43 OD026184-01), Mirimus will develop unique rat models using RNA interference technology, which enables specific genes to be turned on and off in the animal to mimic the effects of small molecule therapies without the drug itself. These animals will enable rapid validation and toxicity assessment even prior to developing drugs, thus they have the ability to curb the enormous R&D expenditures on failed clinical trials. “We are pleased to continue to develop transformative platform
technologies that will enable researchers and drug companies to determine which targets are more likely to have success in clinical trials,” says Dr. Prem Premsrirut,MD/PhD, Co-founder and CEO of Mirimus. “We believe our models are a crucial evaluation tool during the drug discovery process. Many side effects can be treated effectively, but we need to know what to monitor in patients receiving experimental therapies. With these models, we can help pinpoint potential toxicities that will occur in patients and ultimately prevent unnecessary harm.” Gene knockdown by RNAi has been shown to mimic the effects of drug therapy and Mirimus has succeeded in offering custom RNAi mice to researchers for the past 8 years. With new genome editing technologies, it is now possible to engineer this platform in rats, offering a live animal model to fields that prefer rat models. The goal of this SBIR project is to develop a platform for rapid and cost-effective production of RNAi rats, which can be delivered to clients in as little as 4 months. Despite the utility of mouse models, for many scientists, the rat still remains the preferred rodent due to their larger size for surgical manipulation, repeat blood sampling, and their cognitive and physiological characteristics that more closely resemble humans than their mouse counterparts. For neurobiology, cardiobiology, immunology and toxicology, they are still the dominant rodent model in research. We believe that rats will gain popularity once again as the premier rodent model in drug discovery and we intend to be at the forefront of this shifting paradigm. These RNAi rat models will transform the preclinical validation process with assessment of potential drug response and resistance mechanisms in vivo, ultimately guiding the development of safer and more effective drugs. For more information, please contact info@mirimus.com.
Jan. 1, 2017, 9:07 p.m.
Mirimus and Charles River Announce Partnership on CRISPR/Cas9 In Vivo Model Creation Services
Mirimus, Inc. and Charles River Laboratories International, Inc. together expand their mouse engineering capabilities through a strategic partnership. Mirimus, a leader in the creation of RNA interference technology and its use in animal models, has chosen Charles River Laboratories for production of their RNAi mouse models to service their clients with VAF/Elite® quarantine-free animals and provide a full range of drug discovery services globally. In parallel, Charles River Laboratories recently launched their full, end-to-end service offering of CRISPR/Cas9 genome engineering technology. With this technology, Charles River will be able to develop more custom translational research models that will ultimately improve the
efficiency and effectiveness of the drug discovery process. "The combination of Mirimus’ RNA interference and CRISPR/Cas9 genome engineering expertise fused with Charles River’s in vivo model creation services creates a powerful platform for custom model generation,” said Prem K. Premsrirut, MD, PhD, Founder and Chief Executive Officer of Mirimus. "Charles River’s licensing arrangement with the Broad Institute of MIT and Harvard will allow us to rapidly develop novel mouse models, combining the strengths of both CRISPR/Cas9 genome engineering and RNAi technologies, a big step forward for our clients." "Utilizing the CRISPR/Cas9 platform, Charles River clients can work with a single provider for both the in vivo and in vitro phases of their research,” said Dr. Iva Morse, Corporate Vice President, Chief Scientific Officer, Global Research Models and Services at Charles River. “Working with us, clients can generate custom cell lines for early, exploratory discovery research, as well as in vivo pharmacology models, produce those models, and then use our Discovery Services offering to place those models in in vivo studies." Clients engaged in drug discovery can tap into Mirimus experts in creation of RNAi mouse models for early preclinical toxicity assessment and gene target prioritization, to guide early no-go decisions and focus on targets with a promising safety profile. In addition, with this partnership, all clients have access to chemistry, biology and pharmacology experts through the Discovery Services team at Charles River for innovative support and guidance in small molecule drug development expertise across all therapeutic areas. The natural synergy between Mirimus’ molecular biology and Charles River’s embryology capabilities allows Mirimus to deliver study-ready cohorts to meet client project needs and timelines. Charles River’s successful track record in embryology, coupled with their global network of secure breeding facilities and delivery platforms, allows clients to receive their unique genetically engineered models as needed, with no quarantine period.
Aug. 19, 2016, 8:45 p.m.
Global Mice Model (Model, Products, and Services) Market Outlook: 2015-2021
The global mice model and services market is mainly dominated by three main players, namely, Charles River Laboratories, The Jackson laboratories, and Taconic Farms International, Inc. in 2015. Other prominent players in the global market include Harlan Laboratories, Inc., genOway S.A., Covance Inc., Crescendo Biologics Limited, Deltagen, Inc., TransGenic , Inc., SAGE Labs, ImmunoGenes AG, Mirimus, Inc., and Ablexis LLC.
May 27, 2016, 7:35 p.m.
National Institute of Health awards Mirimus with SBIR Phase II Grant- Next generation CRISPR/Cas9-RNAi mouse models for accelerated drug discovery research
Significance: New approaches for rapid identification and early preclinical validation of novel therapeutic targets are crucial to make important “go/no-go” decisions and curb the cost of developing new cancer treatments. Genetically engineered mouse models (GEMMs) are a powerful platform to study disease initiation and maintenance, the tumor microenvironment and the responsiveness of cancers to known or novel therapeutics; however, the long lead times and high costs required to develop, intercross and maintain models with various cancer predisposing gene combinations have limited their practical utility in the drug discovery process. Recently, we have shown RNA interference (RNAi) in mice can serve
as a fast alternative to gene deletion and be exploited experimentally to silence nearly any gene target, by the expression of synthetic short hairpin RNAs (shRNAs). Importantly, because it is reversible, gene silencing by RNAi better mimics the dynamics of small molecule inhibition than permanent genetic knockouts. Furthermore, with the advent of new genome editing techniques, such as CRISPR/Cas9 technology, we are able to introduce additional sensitizing lesions to induce disease pathogenesis. In synergy with RNAi technology, complex multi-allelic ESC based GEMMs can be generated without extensive intercrossing. Using this combination of CRISPR/Cas9 and RNAi technologies, we are able to not only model disease pathogenesis, but also mimic drug therapy in mice, giving us unprecedented capabilities to perform preclinical studies in vivo. Hypothesis: We hypothesize that CRISPR/Cas9-RNAi-GEMMs of cancer can be developed rapidly using new genome editing technologies (CRISPRs) to introduce additional sensitizing lesions and recombinase-mediated cassette exchange (RMCE) for precise integration of tetracycline inducible shRNAs to silence specific gene targets. Preliminary data: We have previously used CRISRP/Cas9 and RMCE to generate RNAi-GEMMs without any breeding. Specific Aims: As a proof-of-concept, we will develop a model of lung adenocarcinoma by using the CRISPR/Cas9 system to introduce a conditional KrasG12D allele into the endogenous locus and in situ delivery of sgRNAs targeting Trp53 which will be activated by a conditionally expressed Cas9 allele. We will further modulate mutant Kras or Mek1/2 activity by introducing tetracycline inducible shRNAs to model therapeutic inhibition. Finally, we will expand our flexible platform by producing validated, ‘off-the-shelf’ viral vectors carrying combination sgRNAs targeting commonly altered genes in NSCLC. Together, these studies will define a new paradigm and accelerate drug discovery research by creating a flexible platform for the generation of RNAi-GEMMs that will serve as innovative research tools, guiding the development of novel and effective therapeutics. The goal of this project is to revolutionize drug discovery research by developing a pipeline for the rapid production of genetically engineered CRISPR/Cas9-RNAi mouse models of cancer – powerful tools with combined features for both conditional gene-specific mutagenesis to drive development of genetically-defined cancers and inducible shRNA therapy to evaluate candidate targets for efficacy and safety, all within the same animal. This transformative platform technology will enable rapid and cost-effective creation of better model systems to identify and validate new targets, predict potential toxicities and ultimately lead to better therapeutic success in our fight against cancer.
April 23, 2015, 6:20 p.m.
RNAi and CRISPR/Cas9-Based In Vivo Models for Drug Discovery
Genetically engineered mouse models (GEMMs) are a powerful platform for enabling the study of disease initiation and maintenance, the microenvironment and the responsiveness of disease to known or novel therapeutics. However, the long lead times and high costs required to develop, intercross and maintain models with various gene combinations have limited their practical utility in the drug discovery process. RNA interference (RNAi) is a rapid, cost-effective alternative to gene deletion that can be exploited experimentally to reversibly silence nearly any gene target not only in vitro, but also in live mice. Mirimus has developed a fast, scalable pipeline for the
production of short hairpin RNA (shRNA) transgenic mice with potent reversible gene-silencing potential. With the advent of new genome editing techniques such as CRISPR/Cas9, it has become possible to introduce additional sensitizing lesions to induce disease pathogenesis. In synergy with RNAi technology, complex multi-allelic ESC-based GEMMs can be generated without extensive intercrossing, resulting in the ability to model disease pathogenesis and mimic drug therapy in mice and enabling unprecedented capabilities for performing preclinical studies in vivo. This webinar demonstrates how Mirimus’ RNAi technology, in combination with CRISPR/Cas9 genome editing, facilitates recapitulation of knockout mice phenotypes and further exploration of potential therapeutic approaches within the same model. This robust system provides a cost-effective, scalable platform for the production of mice with enormous predictive power that will shape development of better-tolerated therapies.
April 20, 2015, 6:21 p.m.
Dr. Prem K. Premsrirut presents RNAi and CRISPR/Cas9 based in vivo models for drug discovery at the AACR Annual Meeting
Genetically engineered mouse models (GEMMs) are a powerful platform that enable the study of disease initiation and maintenance, the microenvironment and the responsiveness of disease to known or novel therapeutics; however, the long lead times and high costs required to develop, intercross and maintain models with various disease predisposing gene combinations have limited their practical utility in the drug discovery process. RNA interference (RNAi), a mechanism that controls gene expression, is a rapid and cost-effective alternative to gene deletion that can be exploited experimentally to reversibly silence nearly any gene target not only in vitro but also in live mice.
By using our “Sensor assay” to biologically identify short hairpin RNAs (shRNAs) that induce potent gene suppression in combination with a new miRNA scaffold, miR-E, we have engineered a reliable system for in vivo gene suppression. Furthermore, by utilizing tetracycline-regulated miR-E based shRNAs with high efficiency ES cell targeting, we have developed a fast, scalable pipeline for the production of shRNA transgenic mice with reversible gene silencing. Recently, with the advent of new genome editing techniques, such as CRISPR/Cas9 technology, we are able to introduce additional sensitizing lesions to induce disease pathogenesis. In synergy with RNAi technology, complex multi-allelic ESC based GEMMs can be generated without extensive intercrossing. Using this combination of CRISPR/Cas9 and RNAi technologies, we are able to not only model disease pathogenesis, but also mimic drug therapy in mice, giving us unprecedented capabilities to perform preclinical studies in vivo. Here, we demonstrate that RNAi in combination with CRISPR/Cas9 genome editing enables us to recapitulate the phenotypes of knockout mice and further explore potential therapeutic approaches within the same model. Using our robust system, we have created a a cost-effective and scalable platform for the production of complex GEMMs with RNAi silencing of nearly any gene - mice with enormous predictive power that will shape our development of better tolerated therapies.
Feb. 19, 2015, 6:22 p.m.
Mirimus Enters Into a Strategic Co-Marketing Alliance with Charles River Laboratories to Provide Superior Mouse Models
Mirimus Inc., a leader in RNA interference technology specializing in the creation of customized genetically engineered mouse models, today announced the formation of a cooperation agreement with Charles River Laboratories that seeks to speed the availability of superior genetically engineered mouse models for the pharmaceutical, biotechnology and academic research communities. Charles River is a leading provider of drug discovery and early-stage development research products and services to global biopharmaceutical and biotechnology companies, government agencies, and leading academic institutions. In this strategic alliance, Charles River will augment its service offerings to the scientific research community through co-marketing Mirimus’ in vitro and
in vivo RNA interference products and services offerings. Mirimus, a company with roots in Cold Spring Harbor Laboratory’s ground-breaking RNAi research, has established itself as a leader in the rapid generation of complex genetically engineered mouse models. “Unlike other RNAi reagent companies, we perform in depth screening of tens of thousands of shRNAs to identify the sequences that will achieve the most potent gene silencing knockdown. Our goal is to significantly advance the drug discovery process. Together, Charles River can offer a full service portfolio that includes the genetic manipulation of research models designed to make them more predictive of the human condition,” said PremPremsrirut, PhD, Mirimus’ President and CEO. Iva Morse, Charles River’s Corporate Vice President for North American Research Model Services, commented, “Our customers are using increasingly complex genetically altered models for greater confidence in the translational potential of their findings, but the time and level of expertise required to create and breed those models in-house can be a real barrier for many labs. Through this partnership, Mirimus’ generates ES cells with shRNAs targeting the gene of interest, and our model creation supportlab performs the microinjection procedures that produce live mice from these cells. This enables our customers to experience the benefits of complex genetic alterations on a much shorter time-scale.” “We are delighted to offer the scientific research community our products and services through Charles River’s global reach,” said Louis Schure, Mirimus’ Director of Business Development. “We are proud to add our RNAi tools to the quality and robust offerings that Charles River provides to the biotech, pharmaceutical and academic research communities. All concerned will benefit from this valued collaboration.”
Aug. 4, 2014, 6:22 p.m.
4National Institute of Health awards Mirimus with SBIR Grant-RNAi mouse models of FAP (Familial adenomatous polyposis)
AIM1: Generate a model of familial adenomatous polyposis using CRISPRs to mutate APC. AIM2: Allow polyps to form and treat mice by Cox-2 inhibition using RNAi to mimic current therapy. shRNA transgenic mice are generated where shRNAs against Ptgs2 are under control of a tet-responsive element and if these mice are intercrossed to mice with ubiquitous expression of the reverse tet-transactivator protein (rtTA), shRNA expression can be induced in all tissues in vivo via administration of doxycycline. Since Apc will have been altered through CRISPR/Cas9 system, Familial Adenomatous Polyposis (FAP) will occur within these mice. We will allow for intestinal polyps to form
and then, administer doxycyline (Dox) to the mice to induce shRNA-Ptgs2 expression to observe the effects of this therapeutic target on the polyps.
Dec. 16, 2013, 6:23 p.m.
An Optimized microRNA Backbone for Effective Single-Copy RNAi
Mirimus develops enhanced tools for reversible gene suppression. The team of ChristofFellmannat Mirimus Inc., Cold Spring Harbor, New York, developed new technology to address the remaining limitations of RNA interference (RNAi), a powerful method that enables functional gene annotation in normal homeostasis and disease. Through an improved molecular design, the scientists at Mirimus were able to suppress target genes with massively enhanced efficiency and accuracy. These results are reported in the recent issue of Cell Reports, published online on December 12th, and will help accelerate drug target identification and validation.
March 29, 2012, 6:24 p.m.
Product focus on RNAi Research
Custom RNAi mouse models developed by Mirimus Inc., which are capable of reversible gene silencing gets featured on the March 29th issue of Nature.
May 20, 2011, 6:24 p.m.
Medical research gets support from local scientists
Researchers at Cold Spring Harbor, PremPremsrirut and ChristofFellmann, have developed a method of gene knockdown in mouse models that has the capacity to revolutionize disease research. Premsrirut and Fellmann’s company, Mirimus, Inc., develops knockdown mice that sell for a fraction of the cost of conditional knockout mouse models.
May 17, 2011, 6:25 p.m.
Mastering RNAi in mice
Dr. Premsrirut and colleagues report new avenues for using mice to model disease. Their method gives researchers the ability to do more complex studies while avoiding time-consuming processes previously required.
May 3, 2011, 6:25 p.m.
$2M in venture capital for LI company
Mirimus Inc., the biotech company started by Drs. PremPremsrirut, ChristofFellmann, Scott Lowe, Gregory Hannon and Stephen Elledge received $2 million in venture capital funding to pursue genetic research that will enable pharmaceutical companies better information regarding disease therapies.