RNAcore

The RNAcore at the Houston Methodist Research Institute is a leader in synthesis of research and clinical-grade RNA constructs for the scientific and medical communities in the Texas Medical Center and across the world. The RNAcore is supported by the Cancer Prevention Research Institute of Texas. We also work with government, NGO and industry to further the development of cutting-edge RNA technologies.

 

As part of the Center for RNA Therapeutics, the RNAcore is on a mission to:

 

  • Perform rigorous research that reveals fundamental insights in RNA biology.
  • Translate those new findings into novel RNA-based products.
  • Assist other academic groups and small companies in developing their great ideas into transformative, clinical grade RNA therapeutics.

 

Core Directors:

John P. Cooke, MD, PhD
RNA Core Medical Director

Murilo T. Domingues Bueno, PhD
RNA Core Scientific Director

RNA Services

The RNAcore is staffed by experienced scientists who design, synthesize, validate, test and encapsulate high-fidelity RNA. We can provide a wide range of generic or customized RNA molecules for any desired species, with various specified modifications for research and clinical-grade, including:

 

  • mRNA
  • modified mRNA (mmRNA)
  • self-amplifying RNA
  • Long noncoding RNA
  • Customized bicistronic constructs
  • Constructs with reporter genes
  • Lyophilization 

Encapsulation Services

We provide RNA Lipid encapsulation (LNP) services as an integral service from idea to delivery.

 

We Can Help You Develop, Manufacture, Deliver and Test Novel RNA Therapies

 

The RNAcore at the Houston Methodist Research Institute recognizes that United States federally funded life sciences entities and funding agencies rely on this attestation before purchasing gene synthesis equipment or products. The RNAcore at the Houston Methodist Research Institute self-attests to its compliance with the US Framework for Nucleic Acid Synthesis Screening. Should this information change, the RNAcore at the Houston Methodist Research Institute agrees to update this statement.

Analytical Services

The RNAcore also provides services for assessing the purity, integrity, and identity of in-vitro transcribed RNA, following GLP (Good Laboratory Practices) guidelines. The following assays are provided on a fee-for-service basis:

 

  • Nucleic acid purity and concentration by UV Spectrophotometry
  • Nucleic acid integrity by Bioanalyzer/TAPE station (microfluidic electrophoresis)
  • Integrity and purity assessment by HPLC
  • Impurity assessment of Residual template DNA by qPCR
  • Impurity assessment of Residual E. Coli DNA by qPCR
  • Endotoxin testing of mRNA samples with the Nexgen-MCS
  • Analysis of size, charge, and encapsulation efficiency of lipid nanoparticles

Helpful Services

Some of our products and services:

Customized vaccines

 

An example of the superiority of mRNA vaccines made by our RNAcore in comparison to the RNA made in an external academic lab as assessed by the immune response of vaccinated animals. Attention to sequence, structure, base modifications, purification, encapsulation and other factors can improve translational efficiency and efficacy of RNA products.

Fully customizable mRNA for any species and any loci

Ongoing RNAcore Research

  • V07-01

    diagram of telomerase therapy

    Telomerase mRNA treatment increases telomere length and reverses most of the stigmata of senescence in vascular cells. We find that iPSC-derived endothelial cells from patients with Hutchison Gilford Progeria Syndrome (HGPS) have shorter telomeres, reduced replicative capacity and function (e.g. ability to generate nitric oxide or form networks in Matrigel), increased release of inflammatory cytokines, aberrant transcriptional profile, abnormal cell and nuclear morphology, and DNA damage. All of these abnormalities are fully or partially reversed by two transfections with mRNA encoding human telomerase. In a murine model of HGPS, overexpression of telomerase using a lentiviral vector also improves vascular function, reduces DNA damage, and mice live longer (see Mojiri A et al, Eur Heart J, 2021).

  • V07-02

    diagram of telomerase therapy

    Transflammation is required for cell fate transitions. Damage- or Pathogen-associated molecular patterns (DAMPs or PAMPs) stimulate pattern recognition receptors such as Toll-like receptor 3 (TLR3) which triggers inflammatory signaling. The inflammatory signaling (mediated by NFkB or other transcriptional activators) causes changes in the expression and/or activity of epigenetic modifiers to increase DNA accessibility. For example, histone acetyltransferase (HAT) expression is increased, thereby augmenting acetylation of histone proteins to increase DNA accessibility. In addition, NFkB increases the expression of inducible nitric oxide synthase (iNOS) which translocates to the nucleus and binds to epigenetic modifiers like the NURD complex, nitrosylating them and reducing their activity. The process of transflammation appears to be necessary for any cell fate transition, in this example a fibroblast to induced pluripotent stem cell (iPSC). (See Lee et al, Cell 2012; Cooke JP, Circulation 2013; Sayed et al, Circulation 2015; Zhou et al, Cell Reports 2016; Meng et al, Circ Res 2016; Sayed et al, Stem Cell 2017; Li et al, Circulation 2019; Chanda et al, Circulation 2019; Meng et al, Circulation 2020)

  • V07-03

    schematic of telomerase therapy

    Transflammation induces a glycolytic shift (increased glycolysis, reduced oxidative phosphorylation) that is associated with mitochondrial export of citrate to the nucleus. There, the citrate is converted to acetylcoA for histone acetylation, to increase DNA accessibility required for cell fate transitions. (See Li et al, Circulation 2019)

  • V07-04

    diagram of telomerase therapy

    Transflammation induces a glycolytic shift (increased glycolysis, reduced oxidative phosphorylation) that is associated with mitochondrial export of citrate to the nucleus. There, the citrate is converted to acetylcoA for histone acetylation, to increase DNA accessibility required for cell fate transitions. (See Li et al, Circulation 2019)

Funding

RNA Core Highlights

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