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Patricia Wongsodirdjo

My research into mRNA-encoded antibodies

I investigate how cells can produce therapeutic antibodies from mRNA, and how to deliver that mRNA to the brain.

My PhD at The Florey and the University of Melbourne focuses on lipid-based carriers for mRNA delivery. My earlier work tested whether mRNA-encoded antibodies could bind tau in human cells.

My mRNA-encoded antibody study

In my first-author study, we used mRNA to produce antibodies that recognise tau, a protein that clumps into toxic aggregates in Alzheimer’s disease. The animation shows how the intracellular antibody fragment is made and binds tau.

See the cell experiments ↓

The cell receives mRNA.

I used synthetic mRNA encoding RNJ1, an antibody that recognises tau. In the cytoplasm, the cell’s protein-making machinery reads this mRNA.

A ribosome reads the mRNA.

A ribosome reads the mRNA from its 5′ end towards its 3′ end, building the protein chain that will form the antibody fragment.

The fragment folds into an intrabody.

The RNJ1 fragment has variable heavy and light domains joined by a flexible linker. These fold into a single-chain variable fragment (scFv) that can bind tau inside the cell.

The intrabody binds tau.

RNJ1 recognises tau’s N-terminus. In our human cell experiments, we detected expression of the mRNA-encoded intrabody and its engagement with intracellular tau.

Illustrated RNJ1 scFv mechanism in human SH-SY5Y cells. Our findings are in Brain Communications (2024).

Our fluorescence microscopy results

We used fluorescence microscopy to compare antibody fragment expression following mRNA and plasmid DNA delivery in neuron-like cells.

  • Tau
  • RNJ1 scFv
  • Nuclei (DAPI)

Following mRNA delivery, our antibody fragment was successfully expressed in the cytoplasm and nuclei of neuron-like cells. Our Z-stack analysis also revealed co-localization with its target, tau.

Human tau-GFP SH-SY5Y cells. Nuclei stained with DAPI. Original published images and scale bars.

Brain Communications (2024), Figure 5A. Full Figure 5 Paper & methods

Imaging courtesy of Alayna Caruso

Expression from mRNA

We expressed RNJ1 scFv from mRNA. Tau and the antibody fragment appear within the same cells.

Published orthogonal Z-stack views of the mRNA experiment, locating tau and RNJ1 scFv within the cell. Original 10 micrometre scale bar.
Our published Z-stack detail also locates tau and the antibody fragment together in the cytoplasm. Published detail · 10 µm

My PhD

mRNA delivery to the brain

I investigate lipid-based carriers to improve delivery of antibody-encoding mRNA to the brain. This builds on my earlier work in mRNA synthesis and extracellular-vesicle delivery.

In the lab, I produce mRNA, synthesise and analyse nanoparticles, culture cells, and measure protein expression and target engagement.

My Dementia Umbrella micrograph: fluorescently labelled human brain cancer cells forming an umbrella-like structure.

Dementia Umbrella. My micrograph of human brain cancer cells used in dementia research, in The Florey Neuropix collection.

Related publications

Full academic record