FAQs

Johns Hopkins University established the RNA Innovation Center in collaboration with TriLink Biotechnologies® to accelerate groundbreaking research in RNA therapeutics. The Center was established in 2024 and is housed in the Whiting School of Engineering at the Institute for NanoBioTechnology (INBT). The INBT is comprised of multidisciplinary faculty whose research spans molecular biology, medicine, engineering, and nanoscience, providing an ideal milieu for exploration of novel RNA therapeutics. The partnership with TriLink affords the Center access to CleanScript^TM, their proprietary state-of-the-art RNA synthesis technology, as well as their technical and cGMP manufacturing expertise. Through the synergy of these academic and commercial pillars, the RNA Innovation Center endeavors to empower investigators to move seamlessly from concept, through discovery, and finally to the cusp of human clinical studies.

The RNA Innovation Center will work with researchers who want to investigate potential RNA therapeutics in preclinical studies. We can be involved at any stage of development from project concept to scale-up of production. For example, we can provide our expertise in the design of RNA molecules to align with the parameters and goals of a project and produce a panel of high quality, validated RNA molecules for testing in a researcher’s assays.

If you’d like to learn more about how we can help you, click on the Contact box at the top of the page.

Some of the obstacles that researchers face when considering mRNA as an investigational option are the scale and the cost. Commercial sources of mRNA molecules may only offer large-scale quantities that far exceed what is required for preclinical studies, or have pricing that inhibits the ability to test a wide variety of RNA candidates. We aim to offer panels of high quality, validated mRNA molecules at a reasonable cost, thus enabling research to develop more quickly and robustly.

Click on the Contact box at the top of the page to tell us a little bit about your project or needs. We will reach out and set up a meeting to discuss your RNA research goals.

RNA, or Ribonucleic Acid, is a naturally occurring molecule found in all living cells and in the environment. RNA’s therapeutic potential has been recognized and investigated for decades. Beyond its medical uses, RNA’s existence long predates humans with evidence suggesting its origin dating back to billions of years ago.

According to the theory of the Central Dogma or Molecular Biology, the flow of genetic information is linear from DNA to RNA to protein. In this framework, RNA works downstream of DNA and and upstream of proteins in the biological assembly line of the cell. Every somatic cell contains the complete set of genetic instructions encoded as DNA, and RNA serves as a messenger, translating these instructions into a format that cells can read to produce specific proteins. Relatively recently, however, RNA was discovered to have a role in regulating gene expression, adding to its already immense known importance in biology. These discoveries were celebrated with Nobel prizes in 2006 for RNA interference and in 2024 for microRNAs.

While RNA shares similarities with DNA, such as being composed of nucleotides that include a sugar backbone, phosphate group, and a nitrogenous base, the key differences include:
Size and Shape: DNA typically exists as a double-stranded helix, while RNA is usually single-stranded. Although some RNA viruses, like rotaviruses, have double-stranded RNA, most RNA viruses (including HIV and all coronaviruses) and RNA in living cells are single-stranded. Additionally, DNA is generally larger than RNA, as RNA is transcribed from only portions of a DNA strand.
Sugar Molecule: RNA contains ribose sugar, which has an additional hydroxyl group compared to the deoxyribose sugar found in DNA. This structural difference makes RNA more reactive, and thus more vulnerable to degradation, than DNA.
Nitrogenous Bases: While RNA and DNA both utilize the nitrogenous bases that contain adenine (A), cytosine (C), and guanine (G), adenine is paired with uracil (U) in RNA, while adenine pairs with thymine in DNA (T).

There are several methods in use to deliver RNA drugs to the human body, as well as much active research focused on optimization and development of new ones. Small oligonucleotide RNA medicines can be delivered using conjugates, but larger RNA molecules, such as mRNA drugs, must be packaged into small particles for successful delivery to the intended target. One common method for packaging uses lipid nanoparticles (LNPs).

LNPs, or lipid nanoparticles, are tiny fat particles that are used to package RNA-based therapeutics. This packaging protects the RNA molecules from degradation when injected into the body. LNPs have variable charges when allow them to move within different portions of the body and cells to ensure the RNA is delivered to the desired target. The use of LNPs over previous delivery systems provides effective mechanisms that can be utilized to safely deliver a wide range of medications.

As with all medications, RNA therapeutics may elicit light to moderate side-effects, but any RNA-based therapeutic that has been approved by the Food and Drug Administration (FDA) has demonstrated its safety and efficacy in clinical trials. FDA-approved RNA therapies undergo the same rigorous inspection and approval process as all other approved medications.

RNA interference (RNAi) is a natural process that silences genes by using small interfering RNAs (siRNAs) or microRNAs (miRNAs) to bind to messenger RNA (mRNA), preventing its translation into proteins. Andrew Fire and Craig Mello were awarded the 2006 Nobel Prize in Physiology or Medicine for discovering RNAi in C. elegans. RNAi has significant therapeutic potential by targeting and downregulating disease-causing genes. The following are some FDA-approved siRNA medicines:

AMVUTTRA (Vutrisiran): Treatment of nerve damage for hereditary transthyretin-mediated amyloidosis (FDA approved June 13, 2022) 

Leqvio (Inclisiran): Reduction of LDL cholesterol in patients with cardiovascular disease (FDA approved December 22, 2021)  

Oxlumo (Lumasiran): Treatment of primary hyperoxaluria type 1 (PH1) (FDA approved November 23, 2020) 

Givlaari (Givosiran): Treatment of acute hepatic porphyria (FDA approved October 20, 2019)  

Onpattro (Patisiran): Treatment of hereditary ATTR amyloidosis with polyneuropathy (FDA approved August 10, 2018)

Antisense oligonucleotides (ASOs) are short, synthetic strands of nucleic acids that complementarily bind to targeted mRNA sequences. This binding blocks protein production from that mRNA and promotes subsequent degradation of that mRNA. ASOs can also modulate alternative splicing by masking certain regions of unspliced mRNA. Antisense oligonucleotides’ high specificity allows them to selectively target disease-causing genes, reducing the risk of effects on unintended targets. This precision helps minimize the chances of disrupting healthy cellular processes and makes ASOs a powerful tool for treating various genetic conditions.

Amondys 45 (Casimersen): Treatment of DMD therapy for patients who can skip exon 45 of the dystrophin gene (FDA approved February 25, 2021)  

Viltepso (Viltolarsen): Treatment of Duchenne muscular dystrophy (DMD) of patients who experience exon 53 skipping (FDA approved August 12, 2020) 

Vyondys 53 (Golodirsen): Treatment of Duchenne muscular dystrophy (DMD) for patients amenable to exon 53 skipping (FDA approved December 12, 2019)   

Exondys 51 (Eteplirsen): Treatment of Duchenne muscular dystrophy (DMD) by skipping exon 51 of the dystrophin gene (FDA approved September 19, 2016) 

Spinraza (Nusinersen): Treatment of spinal muscular atrophy (FDA approved December 23, 2016)

Defitelio (Defibrotide Sodium): Treatment of veno-occlusive disease (VOD) (FDA approved March 30, 2016)   

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas9 is a gene-editing system identified in bacteria and archaea as a defense against viruses. This bacterial immune system was harnessed and engineered by molecular biologists to edit targeted gene sequences with exquisite precision.

This pioneering work on RNA-directed technology revolutionized the field of gene editing and led to the 2020 Nobel Prize in Chemistry award to Jennifer Doudna and Emmanuelle Charpentier.

Casgeny (Exagamglogene Autotemcel): Treatment for sickle cell disease (SCD) and transfusion dependent beta thalassemia (TDT) in patients 12 and older (FDA approved December 8, 2023)

Lyfgenia (Lovotibeglogene Autotemcel): Treatment for sickle cell disease in patients 12 and older with a history of vaso-occlusive events  (FDA approved December 8, 2023)