Leaning into Personalized Healthcare with Nucleic Acid Medicines

December 13, 2017

By: Stephanie Allen

Personalized healthcare is broadly considered treatments and preventions unique for individuals. Precision medicine tends to have a wider reach and focuses on identifying which approaches will be effective for which patients based on genetic, environmental, and lifestyle factors (1). Advances in precision medicine have a foundation in the essential to life substance, nucleic acid, the chemical backbone of RNA and DNA. The topic of a recent program I attended Designing Nucleic Acid Medicines peaked my interest. In this post, I’ll share the highlights with you.

The 4-hour program held on September 13, 2017 at Johnson & Johnson Innovation, JLABS was one installment of the JLABS Science First seminar series. JLABS is an incredible resource for emerging biotechnology companies that provides co-working lab and office space, commercialization curriculum, and access to mentoring and Johnson and Johnson Innovation’s broader network. One of the companies featured in the Sept.13 program, Arcturus Therapeutics, is a JLABS San Diego alumni. Arcturus was founded in 2013 and has continued to grow since its days at JLABS.

Nucleic Acid medicines are just one treatment approach under the larger precision medicine umbrella. Many nucleic acid medicines have been designed to target genetic expression patterns. These patterns have a vast range of diversity. The speakers that presented have a common focus in nucleic acid medicine, but the specific approach and indications they are working on is quite different.

Gene Yeo, is a professor of Cellular and Molecular Medicine at UCSD. He is an expert in the areas of RNA, computational biology, genomics and neurological disease. In his discussion on RNA binding proteins, he talked about their critical role in human development and disease. Spinraza, recently approved for spinal muscular atrophy, is an antisense oligonucleotide drug that blocks the binding of RNA binding proteins such as hnRNP A1 within an intronic sequence, enabling the correct isoform to be spliced. His lab’s recent work mapping the binding sites of hundreds of RNA binding proteins lay the foundation for rational approaches to designing antisense oligonucleotides or small molecule drugs that block the binding of specific RNA binding proteins (2).

In another part of his talk, Professor Yeo focused on a new area of research from his lab that involves using CRISPR to displace RNA binding proteins that target areas dense in RNA repeats that lead to defects in RNA splicing and can cause myotonic dystrophy (DM). Patients with DM have symptoms characterized by progressive muscle wasting and weakness. There are approximately 1 in 8,000 people worldwide affected by DM (3). There is no cure for DM and treatments focus on managing complications related to the disease. Dr. Yeo’s work shows promise for patients that currently have no hope for a better life. The results from their CRISPR approach were impressive. In one study, they found that the expression pattern in 350 biomarkers associated with DM1 was reversed in 94% of the patient muscle samples that had been treated with their CRISPR construct. The work Dr. Yeo presented could be a favorable approach for DM patients considering a new drug in the future. Dr. Yeo’s work is fascinating and demonstrates how academic research can help pave the way to clinically viable products that address unmet needs. Dr. Yeo and other colleagues involved in this work have recently formed a biotechnology start-up named Locanato further develop this technology. One of Locana’s co-founders, Dr. David Nelles, was awarded Biocom’s Life Science Catalyst Award.

Christine Esau, is director of translational biology at Arcturus Therapeutics. Her areas of expertise include microRNA targeting and biology. She has extensive experience in drug development from discovery biology to lead candidate selection from her many years working in cutting edge drug discovery at Isis Pharmaceuticals, Regulus Therapeutics and Aptami Therapeutics. Currently at Arcturus, Ms. Esau oversees siRNA and mRNA therapeutics. The highlight of her talk was the proprietary drug delivery method she discussed. Arcturus has developed a novel biodegradable nanoparticle delivery technology to deliver RNA therapeutics, Lipid-enabled and Unlocked Nucleomonomer Agent RNA, LUNARTM. One of the programs she leads is focused on developing treatment for ornithine transcarbamylase (OTC) deficiency. The treatment involves delivering a mRNA therapeutic using LUNAR to express OTC enzyme. Urinary orotic acid is elevated in Arcturus’s OTC disease mouse model mimicking the conditions observed in human patients. Elevated orotic acid leads to an accumulation of ammonia in the blood causing symptoms that can include vomiting, lethargy, irritability, ataxia, progression to coma and life-threatening complications.

Tu Diep is Vice President of Operations at OncoSec. His areas of expertise include scientific and clinical research. He has been involved across the spectrum of biotechnology from preclinical research, manufacturing and critical roles in securing strategic partners and investment at his previous post with Protox Therapeutics, now Sophiris Bio Inc. Currently at OncoSec, Mr. Diep is Vice President of Operations and oversees day-to-day operations and leads business development efforts. Oncosec’s efforts in novel approaches to cancer treatment are at the epicenter of precision medicine. One of the hallmarks of cancer is its complexity, which includes diverse pathological symptoms, and drug response among patients with the same types of cancer. Mr. Diep’s high-level discussion of technologies being developed at OncoSec revealed that Oncosec is at the forefront of helping cancer patients improve response rate to standard of care treatments and they are early in the development of novel targeting methods to engage the immune system to attack tumors.

Part of Oncosec’s platform is a proprietary electroporation device that injects therapeutics directly into tumor cells. Mr. Diep’s discussion gave us an overview on how injection of DNA plasmids intratumorally activates the immune system to produce immune modulatory proteins that recognize and attack tumors.  Other development efforts at Oncosec are focused on combination therapy that also leverages intratumoral injection and the immune system. Oncosec’s ImmunoPulse IL-12 therapeutic was recently approved for orphan designation and is now being fast-tracked by the FDA. ImmunoPulse IL-12 has been shown to re-sensitize tumors to the checkpoint inhibitor PD-1 therapeutic. Many metastatic melanoma patients receiving PD-1 alone don’t respond, but in combination with ImmunoPulse IL-12 the number of patients responding went up to 48% and 50% of patients had at least one lesion completely disappear. Intratumoral delivery and leveraging the immune system seem to be promising approaches to combatting one of the deadliest of human diseases and Oncosec has established itself as one of the leaders in the path to a cure.

Nucleic Acids are the essential building blocks of life. Alone they are simple macromolecules, but in combination with a myriad of external and internal associations with other small and large biomolecules such as lipids, metabolites and proteins their role in human biology becomes increasingly complex. The speakers have shown us a small snapshot of how important nucleic acids are when we consider their role in the future of precision medicine.



  1. National Institutes of Health, US National Library of Medicine. “What is the difference between precision medicine and personalized medicine? What about pharmacogenomics?” Retrieved from: https://ghr.nlm.nih.gov/primer/precisionmedicine/precisionvspersonalized.

  2. Van Nostrand, EL, Pratt, GA, Shishkin, AA, Gelboin-Burkhart, C, Fang, MY, Sundararaman, B, Blue, SM, Nguyen, TB, Surka, C, Elkins, K, Stanton, R, Rigo, F, Guttman, M, Yeo, GW (2016). “Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP). “13(6):508-14.

  3. National Institutes of Health, US National Library of Medicine. “Myotonic Dystrophy” Retrieved from: https://ghr.nlm.nih.gov/condition/myotonic-dystrophy