Focused ultrasound for treatment of neurodegenerative disease

Neurological disorders present an increasing challenge for an ageing population.  The global incidence of dementia is predicted to reach 82 million by 2030 with up to 80% of those individuals having Alzheimer’s disease (AD).

Researchers at The University of Queensland (UQ) have developed a novel ultrasound technology that can be used in conjunction with microbubbles, which they have shown effectively removes AD pathology and restores memory in animal models.

Unlike drug-based monotherapy, therapeutic ultrasound is not restricted to a single target, resulting in a unique mechanism of action. The UQ team further showed that their prototype technology is a tool for non-invasive intracerebral delivery of therapeutic antibodies.  The technology has the potential to address the unmet need in neurodegenerative disease treatment, in addition to being an attractive solution for improving the delivery and effectiveness of pipeline neurological therapeutics.

Key features

  • Non-invasive technology for treatment of brain diseases including Alzheimer’s disease
  • Investigational Use Only clinical research platform, ready for 2022 first-in-human study
  • Functional data in small and large animal models showing restoration of memory
  • Transient blood-brain barrier (BBB) opening resulting in >10-fold increased uptake of therapeutic antibodies
  • Improved cognitive function in healthy aged animals post-treatment without the need for BBB opening.


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Method for stable integration of genes that boosts product expression in yeast

Yeast-based expression systems are commonly used to produce both recombinant proteins and small molecules. Overexpression of a gene by increasing its copy number is generally desirable, but that copy number (and therefore yield) is often traded for other important factors such as growth efficiency and/or unstable modifications.

Researchers at The University of Queensland (UQ) have developed a technology for targeted and stable integration of a gene of interest in a manner that affords control of copy number and – when tested on a range of target genes in S. cerevisiae – increased protein expression compared to standard yeast systems.

Key potential benefits

  • Increase expression yields of small molecules and recombinant proteins by amplifying gene copy number
  • Targeted and stable genomic integration of construct(s) without harsh selection conditions
  • Compatibility with many synbio circuits for auto-induction of protein expression
  • Proof-of-concept data in yeast, but potential application in other cell-based expression systems.

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Modulators of Class IIa HDACs

Histone deacetylases (HDACs) are enzymes that mediate the removal of acetyl groups from numerous acetylated proteins (including histones) and some are associated with the cell cycle, inflammation, apoptosis and cancer. HDACs have been found to be involved in a wide range of diseases and conditions and represent promising drug targets.  There are eleven zinc-binding mammalian HDACs including 4 class I, 4 class IIa and 2 class IIb proteins.

The Fairlie Research Group at The University of Queensland (UQ) has exploited structural differences between Class I and IIa HDACs to develop two generations of new compounds that are potent and selective inhibitors of class IIa HDACs.

Inhibitors of Class IIa HDACs have the potential to treat many inflammation-related pathologies.

Key features

  • New potent and selective inhibitors of class IIa HDAC enzymes
  • No induction of cellular histone H4 acetylation, unlike most inhibitors of HDACs
  • Potential for modulating class IIa HDAC functions in vivo with fewer cytotoxic side effects than other HDAC inhibitors.


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Clec9a targeted vaccination for virus-mediated autoimmune disease

Growing evidence is now associating the development of auto-immune disease with poor chronic viral control, including:

  • Rheumatoid arthritis: associated with increased EBV viral load and expanded viral-specific T cells;
  • Multiple sclerosis: high prevalence of EBV at disease onset, cross-reactive pathogenic antibodies identified;
  • Sjogren’s syndrome: high EBV and CMV viral load, viral-specific T cells.

Vaccination against viruses such as EBV and CMV in the early stages of disease could intercept progression of, or potentially cure, a range of autoimmune diseases.  Eliciting an appropriate immune response is key, with the goal to manage viral control as opposed to viral elimination.

Researchers at The University of Queensland (UQ) have developed a technology: liposome nanoparticle targeted to human CD141+ DC-1 cross-presenting dendritic cells that selectively express clec9a through a novel clec9a-targeting peptide.  Targeted liposomes effectively deliver tailorable payloads and induce specific cytotoxic T-lymphocytes without requiring adjuvant.

Proof of concept

Data for clec9a-targeted delivery with prototype nanoparticles (nanoemulsions) demonstrates successful delivery of payloads to human CD141+ DC1 populations.

Key features

  • Novel approach to deliver bespoke, tailorable payloads to dendritic cells
  • Self-adjuvanting liposomes generate robust CD4+ and CD8+ responses to payloads
  • Proposed to prevent progression of viral-associated autoimmune diseases.


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IBD therapeutic derived from gut microbial metabolites

Inflammatory bowel disease (IBD) is a chronic and incurable disease characterised by episodic and disabling inflammation of the gut.  Current therapeutic strategies aim to decrease the frequency and severity of inflammatory episodes to prevent progression of bowel damage and avoid disabling disease with need for surgery.  However, these therapeutic options suffer from poor compliance, toxicity or cost.

There is an urgent need for better therapeutics.  With clear evidence that intestinal immunity is regulated through microbiome-immune crosstalk, the microbiome has now emerged as a valuable potential source for immune-modifying IBD therapeutics.

Researchers at The University of Queensland (UQ) have isolated gut bacteria that secreted soluble suppressors of the pro-inflammatory NF-κβ pathway, and identified a novel class of NF-κβ inhibitory bioactives.  Based on the bioactives, a lead compound – ‘Compound HC’ – with potent NF-κβ activity (IC50 = 1 nM) was synthesised.

Preliminary pharmacokinetic profiling in mice shows that Compound HC is detectable at active concentrations throughout the ileum and colon less than 1 hour following oral administration and remains at concentrations >100×IC50 for >6 hours.

Key features

  • Leverage benefits of microbiome to treat IBD
  • Novel molecules potently inhibit NF-κβ pathway throughout the colon
  • Comparable reduction in disease severity to biologic therapies
  • Orally active, with >6 hours gut stability and favourable PK profile.


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The future of copper production

Researchers at The University of Queensland have developed a new approach to copper production. It is widely applicable and suited to around 70% of all copper reserves. Processing the copper ore onsite avoids the CO2 emissions and other costs of transporting the ore for smelting – instead this is carried out at the mine site to produce a higher value copper intermediate product.

The technology is based on an electrowinning approach but runs at higher efficiency with lower energy usage compared to traditional electrowinning. The power required for the electrowinning can be provided by onsite renewable energy generation.

The technology provides the following value to its users:

    • Reduced OPEX: Significant energy savings versus conventional electrowinning as more than half the energy for Cu EW is associated with oxidation of water.
    • CAPEX savings: Simpler hydrometallurgy process flowsheet (Leach-SX-EW) versus (Slurry EW) and no need for high temperature copper smelter/converter.
    • Clear separations of Cu, Co and Au allowing for efficient recovery of all three metals of interest.
    • Low environmental footprint (Low CO2 if renewable electricity, no smelter gas, largely benign solids residue, opportunities for water recycling).

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Controlled release nano-termiticide formulation

Chemical treatment is used extensively to protect buildings from termite infestation.  Current termiticide formulations have faced several limitations that influence their termiticidal efficacy, for example limited soil penetration capacity and limited (<15 years) lifetimes.  Therefore there is a need for a long-life chemical barrier technology that can better penetrate soil, and which possesses the ability to become active only after a period of weeks following application to ensure termites escape the building prior to activation.

Researchers at The University of Queensland have developed a nano-formulation technology that has the potential to solve the application and synthesis problems described.  The technology utilises a cheap, commercially available precursor material that avoids the need for expensive surfactants or chemical reactions.  The nano-formulation technology has a high loading capacity of active ingredient in its nano-dispersed form (ie no aggregation/formation of large crystals is observed).  The technology can be used to precisely control the release rate and can enhance the soil penetration of the active ingredient.

Key Features

  • Scalable, cheap and facile synthesis of nano-termiticide formulations
  • High loading capacity of active ingredients without aggregation/crystallisation
  • Applicable to different active ingredients, eg bifenthrin, fipronil
  • Precisely controllable release rate and enhanced soil penetration.

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Peptide activator of ACE-2 for kidney diseases and inflammation

The prevalence of diabetes mellitus continues to increase in both Australia and worldwide and it remains the number one cause of chronic kidney disease.  There are currently no treatments for diabetes induced kidney fibrosis and current treatments for diabetic nephropathy only slow down the disease progression, with the patients still progressing to end-stage renal disease and requiring renal replacement therapy.

University of Queensland researchers have developed a 10 amino acid ACE-2 stimulator peptide derived from snake venom useful for the treatment of kidney diseases and inflammation.  Preliminary data demonstrated that the lead peptide 2A has strong anti-inflammatory effects and prevents the expression of markers of fibrosis and inflammation in culture cells.  2A also attenuated kidney fibrosis and inflammation in diabetic mouse models and reduced blood glucose levels without any effect on body weight.

Key Features

  • ACE-2 stimulator with strong anti-inflammatory effects
  • Stable: peptide detected in multiple organs after 24 hours
  • Safe: no observed adverse effects in diabetic mice.


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Knock-in genetic barcodes for multiplexed single-cell sequencing

To overcome the high cost of processing single-cell RNA sequencing, multiplexing methods have emerged that accelerate knowledge gain in gene and drug discovery.  Development of genetically encoded barcodes in isogenic cell lines overcome key limitations with existing barcoding methods.

Researchers at The University of Queensland (UQ) have generated a method for barcoding human cells with proprietary barcodes that enables scalable multiplexed single cell RNA sequencing.  The UQ technology platform provides trillions of barcoding options for engineering any human cell line, enabling a significantly expanded portfolio of experimental design options not possible with external barcoding methods.

Key features

  • Trillions of unique barcodes options
  • No expensive single-use reagents needed
  • Simpler workflow and improved results compared to commercial multiplexing methods
  • Expanded portfolio of experimental designs.


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