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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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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CAST gene editing platform

While CRISPR-Cas9 is a powerful tool that has become the method of choice for genome editing, it is known to introduce unwanted ‘on-target’ and ‘off-target’ mutations, limiting its utility.  Cas9-gene editing relies on the introduction of DNA double strand breaks that cause unwanted and potentially deleterious mutations and deletions at both on-target and off-target sites in the genome.  Other versions of CRISPR-Cas9 (such as single base editors) were developed to address this, but are not suitable for applications aimed at introducing exogenous genes, and generally suffer from the same lack of specificity as normal CRISPR-Cas9.

Researchers at The University of Queensland (UQ) have developed a novel genome editing platform that virtually eliminates mutagenesis, yet has comparable efficiency to conventional CRISPR-Cas9.  It can be delivered using a plasmid in the same manner as CRISPR-Cas9, requiring no changes to current gene editing practices.

Key features

  • Enables genomic integration of heterologous gene sequences or single base editing
  • Comparable editing efficiencies to the conventional CRISPR-Cas9 system with vastly reduced error rates in targeted locus
  • Virtually undetectable on-target indels (Insertions deletions) at site of gene insertion
  • Provides greater flexibility in where gRNA needs to target – enabling optimised gRNA design and targeting of difficult genomic loci.


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Advanced bioscaffolds for dental applications

Advanced biomaterials for orofacial regeneration and augmentation

The incorporation of inorganic fillers within polymer matrices for the purposes of either increasing bioactivity or enhancing mechanical properties remains a significant practical challenge.  Current approaches for producing bioactive scaffolds predominantly lead to heterogeneous filler dispersion, resulting in variability of bioactive and mechanical properties throughout the scaffold and poor manufacturing reproducibility.

Researchers at The University of Queensland’s School of Dentistry have developed a novel method for solvent-free homogeneous mixing of bioactive inorganic nanofillers within biodegradable scaffolds.  The technology enables the production of fully resorbable ‘patient-specific’ or ‘off-the-shelf’ scaffolds for bone regeneration and augmentation of sinus, periodontal and large-volume vertical alveolar bone defects.

Key features

  • Novel method for producing bioactive biodegradable tissue scaffolds
  • Enables patient specific dental implants with enhanced mechanical and biological properties
  • Fully resorbable scaffolds, eliminating need for implant removal surgery
  • POC demonstrated in a sheep extraskeletal bone formation model.


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Silica nanocapsules

Silica micro-nanocapsules for controllable sustained release of active ingredients, including delicate biologics.

Designed peptide or protein surfactants are used typically to generate an oil in water nanoemulsion.  The surfactant also incorporates a mineralising peptide sequence.  In the presence of a silica source, this mineralising component facilitates the formation of a silica shell to encapsulate the nanodroplet containing the active ingredient. The nanometer thickness of the silicate shell can be regulated which, in turn, allows the rate of active ingredient release to be controlled if required.  This encapsulation technology has been applied to coating microbes and could be used to protect them from processing or storage conditions.

It is also possible to control the surface chemistry and texture – there is scope to initiate release in response to pH.

Initial cost analyses suggest that this encapsulation approach will be low cost.

Potential applications

  • Agriculture, veterinary, pest control, functional packaging
  • Sustained or triggered release of active ingredients, including small molecules and bioactives
  • Encapsulation of delicate actives (eg microbes) to provide temporary protection prior to release.


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Rapid DNA readout system

The ability to amplify and detect specific DNA sequences is a powerful tool routinely used for a wide variety of applications, including disease diagnostics and mutant screening. With the development of isothermal DNA amplification methods, such as loop-mediated isothermal amplification (LAMP), the need for expensive laboratory thermocyclers for molecular-based diagnostics has now been eliminated. However, the requirement for low-lost, simple and equipment-free DNA readout methods remains.

Researchers at the University of Queensland have developed a rapid method to visualise amplified DNA in just one-step, without requiring any equipment. The readout system is made possible by a unique combination of suspended nanoparticles within a special DNA-detection solution.

Key features

  • Detects amplified DNA in 10-30 seconds
  • Equipment-free – results read by the naked eye
  • Amplification and detection performed in a single tube
  • Ideal for point-of-need diagnostics.


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Self-assembling, self-adjuvanting system for delivery of peptide-based vaccines

Researchers at the University of Queensland have developed a novel peptide-based immunogenic agent that facilitates self-assembly with peptide epitopes into an immunogenic complex that has adjuvant properties, therefore obviating the need for external adjuvant or other general immune stimulants. The immunogenic agent comprises a peptide covalently coupled or conjugated to one or more peptide epitopes. The compounds produced self-assemble into distinct nanoparticles as well as chain-like aggregates of the nanoparticles under aqueous conditions.

Key features

  • Fully defined, peptide-based, self adjuvanting single molecule for the delivery of peptide vaccines without the need for additional adjuvants or other immune stimulants
  • Capable of self-assembly into nano/micro particles and are non-toxic and biodegradable
  • Capable of inducing strong specific protective immune responses in Group A Streptococcus (GAS) and human papillomavirus (HPV) in mouse models
  • Platform technology is adaptable for any peptide-based vaccine.


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Automated Topology Builder

Accurate force field parameters for molecular modelling

The Automated force field Topology Builder (ATB) facilitates the generation, validation and refinement of force field parameters for use in molecular modelling applications such as the simulation of biomolecular systems (e.g. proteins, lipids, nucleic acids, and carbohydrates), predicting the morphology of novel material (e.g. organic semi-conductors) and computational drug design.

The ATB utilises data from quantum mechanical calculations including the 3D optimised geometry, electrostatic potential energy surface and the Hessian in conjunction with molecular graph analysis to assign parameters and generate all atom and united atom topology files for use in a range of modelling packages including GROMOS, GROMACS, LAMMPS, CNS, Phenix, Refmac5, as well as APBS.

Key features

  • Consistent and transferable parameters achieving high accuracy and predictive power with fewer terms
  • Robust, well validated and transparent parameterisation strategy
  • Predictive over large datasets without use of molecule specific scaling factors
  • ATB algorithm optimised using database of over 250,000 drug-like molecules.


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High loading core shell nanoparticles

Approximately 40% of approved drugs and 90% of pipeline drugs exhibit poor water solubility, which often leads to low drug efficacy.  In biomedical applications, biodegradable polymer nanoparticles can be particularly useful in formulating poorly soluble drugs for improved bioavailability, safety, tolerability and efficacy.  However, among various polymer nanoparticle systems, drug loading is usually below 10% which hinders their practical applications.

Researchers at The University of Queensland have developed new approaches for the synthesis of polymer (eg. PLGA, PLGA-PEG, PLA-PEG, shellac) nanoparticles encapsulating insoluble small molecule drugs (eg. paclitaxel, docetaxel, curcumin, amphotericin B, Scutellarin, Bulleyaconitine A, ibuprofen, ketamine, imaging agents Dil and DiO).  These methods allow for the improved control of polymer formation around drug nanoparticle cores whilst avoiding the formation of aggregates.

Key features

  • Preparation of core-shell nanoparticles with up to 58.5% drug loading
  • Simple, reproducible method that enables good particle size control and stability.

Potential application

  • Encapsulation of insoluble small molecule drugs
  • Formulation of active ingredients for animal health and agrichemical applications
  • Encapsulation of imaging agents.


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Novel constructs for flavivirus vaccines and diagnostics

Researchers at The University of Queensland have developed a new chimeric virus platform suitable for use in flavivirus vaccine and diagnostic applications.

Key features

  • Chimeras combining an insect-specific flavivirus (ISF) genomic backbone with specific antigenic elements of a vertebrate-infecting flavivirus (VIF)
  • ISF chimeras replicate only in mosquito cells and are expected to be safe to administer to humans and can be prepared with minimal biocontainment
  • Data shows diagnostic and vaccine applications with strong antigenic authenticity
  • ISF chimeras successfully designed to display the antigens from a range of flavivirus pathogens including dengue fever and Zika.

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