PhaRNA Laboratory

PhaRNA, LLC, a biotechnology company headquartered in Houston, TX, is founded by PhD scientists and entrepreneurs who have substantial expertise in the design and application of pharmaceutical products, including small molecules and long (>150 b) RNA products.

PhaRNA blends the broad expertise of its founders to innovate the design and production of RNA for basic and translational research including preclinical, clinical, cosmetic and veterinary applications.

Our state-of-the-art, R&D RNA laboratory allows us to provide premier quality RNA products for pre-IND and IND-enabling efficacy and toxicity studies.

PhaRNA has the world’s largest archive of messenger RNA mimetic (mRNA mimetic) products for research and development activities. PhaRNA’s mRNA mimetics represent natural mRNA analogs or modified messenger RNA (mmRNA) transcripts. PhaRNA, LLC specializes in the design and synthesis of long (>150 b) RNAs including Fusion and/or Bi-/Poly-cistronic mRNA mimetic constructs as well as long non-coding RNA (lncRNA) products.

Scientific Leadership

Eduard Yakubov, Ph.D.

Chief Scientific Officer
& Co-Founder

Dr. Eduard Yakubov is Chief Scientific Officer and one of the founders of PhaRNA, LLC. Dr. Yakubov received his Ph.D. degrees in Neurobiology from Weismann Institute of Science (Israel). Before foundation of PhaRNA, LLC Dr. Yakubov worked as Director of RNAcore facility at Houston Methodist Research Institute (HMRI) and was Assistant Research Professor of Biochemistry at HMRI with a joint appointment as an Assistant Research Professor of Biochemistry at Weill Cornell Medical College (WCMC). Prior to Methodist, he received extensive training at Weismann Institute of Science (Israel) and Stanford University, School of Medicine.

Dr. Yakubov’s postdoctoral work has been focused on the reprogramming of adult fibroblasts into induced pluripotent stem cells (iPS cells), using the mRNA of several transcription factors. His efforts for being first to demonstrate the feasibility of mRNA as a reprogramming molecule were summarized in a Feb. 2010 BBRC publication. Currently this innovative concept and method is positioned to be the main road in cell fate regulation and reprogramming.

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As Director of the RNAcore Facility at Houston Methodist Research Institute, Dr. Yakubov led the operation of the facility and provided RNA services to support scientific initiatives for all members of the Texas Medical Center (Houston), the Progenitor Cell Biology Consortium (involving approximately 31 leading Universities around the United States as well as in Canada and Germany) at NIH-NHLBI, and other academic institutions worldwide.

Dr. Yakubov’s scientific efforts have been focused on using the modified mRNA approach to transiently express telomerase in human somatic and adult stem cells. This innovative mmRNA-based approach providing safe (not virus or plasmid DNAs based which can cause insertional mutagenesis and cancer) and transient (does not immortalize treated cells) telomere extension may find immediate use in increasing the replicative capacity and decrease senescent phenotype of therapeutic cells during their ex vivo safe modification and expansion. In the future, the technology might be useful for cell therapy and human body therapeutic regeneration and rejuvenation.

Dr. Yakubov’s Contributions to Science

  • First to demonstrate that somatic cells can be reprogrammed using RNA (“Reprogramming of human fibroblasts to pluripotent stem cells using mRNA of four transcription factors” (Yakubov et al., BBRC 394/1, 2010 Feb 25). As a post-doctoral scholar in the lab of Dr. David Givol again at the Weizmann Institute of Science (Israel), Dr. Yakubov made the seminal discovery that somatic cells could be reprogrammed using mRNA, subsequently validated by the Harvard investigators led by Dr. Rossi.  His approach is rapidly becoming the gold standard for generation of insertion-free patient specific induced pluripotent stem cells (iPSCs).
  • First use of mRNA encoding telomerase reverse transcriptase (TERT) to extend telomeres in human cells rapidly and safely. As a senior scientist at Stanford University, Dr. Yakubov, in collaboration with Drs. John Ramunas and Helen Blau, demonstrated that in vitro delivery of mRNA encoding TERT to human somatic cells extends telomeres rapidly so that the treatment can be brief, after which the protective telomere shortening mechanism remains intact.  (Ramunas, Yakubov et al., FASEB J., Vol.29, May 2015).  Because telomere shortening is implicated in major human age-related pathologies including cardiovascular, immune diseases as well as loss of skin integrity this technique has important implications for both prevention and treatment.
  • Key role in identifying the role of innate immunity in cell reprogramming (Lee et al., Cell, 2012). While at Stanford, Dr. Yakubov co-discovered that retroviral vectors and mmRNAs used in nuclear reprogramming are more than mere vehicles for delivering transcription factors, but rather they induce global changes in cellular gene expression and activity of epigenetic modifiers that support the reprogramming process.  This discovery resulted in a new class of mmRNA related innate immunity modifiers (Stanford’s OTL patent application), allowing efficient mRNA-based somatic cell reprogramming into iPSCs or direct transdifferentiation of cells into other cell types.
  • Key role in use of mRNA to induce the formation of haematoendothelium directly from human pluripotent stem cells (hPSCs). In collaboration with Drs. Elcheva and Slukvin at the University of Wisconsin, Dr. Yakubov designed tailored RNA constructs encoding transcription regulators ETV2 and GATA2 for direct reprogramming of ESCs and iPSCs into haematoendothelium while at Stanford. Results of this study provided the clear evidence that brief expression of ETV2 and GATA is sufficient to commit hESCs to blood fate (Elcheva et al., Nature Communications, 2014).

Yohannes Ghebre, Ph.D.

 Co-Founder & Scientific Advisor

Dr. Yohannes T. Ghebre is Associate Professor and Director of Radiation Biology Laboratory in the Department of Radiation Oncology at Baylor College of Medicine (BCM). Before joining BCM, Dr. Ghebre was Assistant Professor of Cardiovascular Sciences at the Houston Methodist Research Institute (HMRI) with a joint appointment as an Assistant Professor of Pharmacology at Weill Cornell Medical College (WCMC). Prior to Methodist, he received extensive training at Stanford University, School of Medicine.

During his 6 years of training at Stanford University, Dr. Ghebre made substantial contribution towards our understanding of endogenous and exogenous factors that regulate the nitric oxide synthase (NOS) pathway including their influence on the vascular endothelial system. In addition, he has made important contribution in the discovery and characterization of small molecules that modulate nitric oxide levels in the settings of tissue inflammation and fibrosis. In this regard, his work with Proton Pump Inhibitors (PPIs) has been featured in International Media outlets including The Wall Street Journal; Forbes Magazine; The New York Times; Washington Post; The Guardian; Science Daily; Daily Mail (UK); and Front Page of the Houston Chronicle.

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For his scientific excellence, Dr. Ghebre has received numerous awards including two merit-based postdoctoral fellowships, the Caroline Wiess Law Translational Research Grant, and merit-based grants from the American Heart Association (AHA) and the National Institutes of Health (NIH). Dr. Ghebre currently runs an NIH-supported laboratory at Baylor College of Medicine to evaluate the efficacy of candidate small molecules in mitigating tissue inflammation and fibrosis.  Dr. Ghebre has published over 30 peer-reviewed articles, reviews, editorials and book chapters which have been collectively cited over 1,000 times.

In addition to his research duties, Dr. Ghebre is involved in several academic activities including education, service in committees including with the American Thoracic Society, and peer review of manuscripts and grants. He is also a fellow of the American Heart Association (FAHA).

As a scientist-entrepreneur, Dr. Ghebre is Co-Founder and Advisory Committee Member of PhaRNA, LLC.

Advisors

Eric Eastman, Ph.D.

Scientific Advisor

Dr. Eric Eastman is a strategic business consultant to a variety of biotechnology, biopharmaceutical and technology companies with more than 36 years of research experience and 30 years in senior management positions at various biotechnology and biopharmaceutical companies. He has previously held positions as Co-founder and Chief Science Officer at DioGenix, where he managed the development of molecular diagnostic tests for immune-mediated neurological diseases including multiple sclerosis; Vice President for Diagnostic Ventures at Gene Logic (2005-2008), where he managed biomarker discovery projects for diseases including multiple sclerosis, Parkinson’s disease, depression, and a variety of metabolic diseases; Chief Operations & Scientific Officer of Genetraks, an Australian-based veterinary molecular diagnostics company; Senior Vice President and Chief Scientific Officer at MetriGenix (now Axela), where he  was responsible for the development of molecular diagnostic tests using the company’s Flow-thru ChipÔ or Ziplex platform; President of Morphochem, Inc. (the U.S. subsidiary of Morphochem AG, headquartered in Munich Germany), where he oversaw the identification of genomic biomarkers for use in the company’s small molecule drug development programs;

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Vice President and Chief Technology Officer at Gene Logic (1996-2001), where he had operational responsibility for all laboratory operations and R&D activities supporting the company’s drug target discovery programs and database products; Director of the Gene Expression, Process R&D, and Manufacturing groups at GeneMedicine (later Valentis), where he directed the development of cell- and tissue-specific gene expression systems for the company’s non-viral gene therapy programs.  He also directed the development of the first scalable cGMP manufacturing process to produce plasmid DNA for human gene therapy applications. Prior to joining GeneMedicine, he was Vice President and Chief Scientific Officer of Lark Sequencing Technologies (eventually acquired by Beckman Coulter and now part of GENEWIZ); and Director of Molecular Biology and Immunoassay Development at BIOTX.

Dr. Eastman received his M.Phil. and Ph.D. degrees in Human Genetics and Development from Columbia University College of Physicians & Surgeons (New York, NY); M.S in Genetics from the University of Connecticut (Storrs, CT); and B.S. from Middlebury College (Middlebury VT).

Dr. Eastman has served on the Board of Directors and Scientific Advisory Boards for a number of U.S.-based and International early stage biotechnology companies.

Glenn Hoke, Ph.D.

Scientific Advisor

Over the past 25 years, Dr. Glenn D. Hoke has help establish and grow early stage biotechnology companies .  He was on the initial scientific team at Ionis Pharmaceuticals, led drug discovery and development for Dyad Pharmaceuticals, managed technology assessment and product development at Gene Logic, and, as CEO at Theranostics Health, established a diagnostic testing business providing pharmaceutical services and therapy guiding CAP/CLIA tests to oncologists.  Glenn has experience in pharmaceutical discovery and development, genomic and proteomic technology assessment and brings to Pharna a background in nucleic acid chemistry focused on applications as reagents and therapeutics.  Dr. Hoke received his Ph.D. in Biochemistry from Virginia Commonwealth University’s Medical College of Virginia.

PhaRNA Scientists’ Selected Publications Using unmodified and modified mRNAs

  • John Ramunas*, Eduard Yakubov*, Jennifer J. Brady, Stéphane Y. Corbel, Colin Holbrook, Moritz Brandt, Jonathan Stein, Juan G. Santiago, John P. Cooke, and Helen M. Blau. Telomere extension and increased proliferative capacity following transient delivery of modified mRNA encoding TERT to human cells. (FASEB J. 2015 Jan; 29(5):1930-9; *these authors contributed equally to this work. FASEB.
  • Irina Elcheva, Vera Brok-Volchanskaya, Akhilesh Kumar, Patricia Liu, Jeong-Hee Lee, Lilian Tong, Maxim Vodyanik, Scott Swanson, Ron Stewart, Michael Kyba, Eduard Yakubov, John Cooke, James A. Thomson, and Igor Slukvin. Direct Induction of Hematoendothelial Program in Human Pluripotent Stem Cells by Transcriptional Regulators. Nature Communications. Published 14 Jul 2014, DOI: 10.1038/ncomms5372
  • Jieun Lee, Nazish Sayed, Arwen Hunter, Edward Mocarski, Eduard Yakubov, ReneeReijo Pera, John P. Cooke. Activation of Innate Immunity is Required for Efficient Nuclear Reprogramming. Cell 151, 547-558, October 26, 2012
  • Yakubov E, Rechavi G, Rozenblatt S, Givol D., Reprogramming of human fibroblasts to pluripotent stem cells using mRNA of four transcription factors. Biochem Biophys ResCommun. 2010 Mar 26;394(1):189-93. Epub 2010 Feb 25

Recent Scientific Reports Using PhaRNA modified mRNA (mRNA mimetics)

PhaRNA Scientists’ Recent Review Related to RNA Therapeutics

  • Yohannes T Ghebre, Eduard Yakubov, Wing Tak Wong, Prasanna Krishnamurthy, Nazish Sayed, Andrew G Sikora and Mark D Bonnen. Vascular Aging: Implications for Cardiovascular Disease and Therapy. Translational Med (Sunnyvale) 2016, 6:4 DOI: 10.4172/2161-1025.1000183.