Hong Moulton, PhD

Professor, Senior Research - Chemistry and Antisense Drug Delivery

Office: 541-737-6954
Fax: 541-737-2730

Dryden Hall

Dryden Hall 212A

450 SW 30th Street

450 SW 30th Street
Corvallis, OR 97331

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Affiliated with: 
Veterinary Medicine
OSU Main Campus
Research/Career Interests: 

Moulton Laboratory Website

Morpholino antisense oligos block sites on RNA and can make targeted changes in gene expression. Morpholinos have been widely used in developmental biology to bind RNA transcripts in embryos of model organisms. In embryos, Morpholinos can be conveniently delivered by microinjection into the cytosol of early zygotes. This has demonstrated the power and flexibility of the Morpholino approach when delivery is not an issue. In adult animals, the delivery challenge has inhibited widespread application of Morpholinos. Morpholinos have been slow to enter the pharmaceutical field as pharmacologically active compounds. This is largely due to their poor uptake across the plasma membrane of cells. There are several FDA-approved Morpholino oligo drugs, but so far these are limited to treatment of Duchenne muscular dystrophy (DMD). In DMD regenrating muscle fuses with satellite cells that have taken up Morpholinos, delivering small doses of the oligos to the site where they are needed for therapeautic effect. To apply Morpholinos with better efficacy for DMD and more broadly in human diseases, good techniques for enhancing their delivery in vivo are needed. There is another need for effective delivery of Morpholinos into bacterial cells without toxicity to human cells, allowing therapeutic targeting of Morpholinos to bacterial diseases. Other applications involve targeting Morpholinos for uptake into different animals, such as our current work on enhanced Morpholino delivery into corals to study the mechanisms of coral disease. 

My long-term research interest is to improve delivery of Morpholinos into cells in adult tissues, enabling the therapeutic use of Morpholinos for treatment of a broad range of diseases. Chemical structures have been found which, when linked to a Morpholino oligo, enhance the delivery of the Morpholinos from blood into the cytosol of cells. I invented a class of compounds, the peptide-linked Morpholino oligos (PPMO), which are in clinical trials and are the workhorse molecules produced in my laboratory for many applications for eukaryotic and prokaryotic systems. I am also studying alternative strategies for enhancing Morpholino delivery in vivo by other chemical modifications and formulations. 

PPMOs designed and produced in my lab have been investigated for the following applications: 

Eukaryotic systems: 

  • Host and pathogen interactions
  • Genetic diseases, including cyctic fibrosis, spinal muscular atrophy, Duchenne muscular dystrophy
  • Viral pathogens, includin SARS-CoV2, Lasse virus, influenza virus, and dengue virus
  • Multiple sclerosis
  • Cancers

Prokaryotic systems: 

  • Bacterial pathogens that cause coral, oyster, and citrus greening diseases