Biomanufacturing Research Group

Comparative Analysis of VLP and LNP-Based Delivery System

Primary investigator:

Mr Xiaoyan Wang
xiaoyan.wang@adelaide.edu.au
Mr Xiaoyan Wang's Researcher Profile

Project abstract:

Delivery of nucleic acids through nucleic acid delivery vehicles for the treatment of tumours is one of the current emerging strategies for tumour therapy. Lipid nanoparticles offer improved in vivo gene biodistribution and pharmacokinetic profiles, rendering them a favourable approach for clinical trials. Concurrently, virus-like particles, in addition to the vaccine properties they possess, are gradually being recognised for their special properties as gene carriers due to their unique nanostructures. However, applied research in the use of virus-like particles as vectors for tumour therapy is still relatively limited compared to the research into virus-like particles as vaccines. To address these challenges, this project aims to investigate RNA-loaded virus-like particles as a potential nucleic acid delivery system for RNA therapy and cancer treatments. The project starts with developing efficient methods for packaging RNA into virus-like particles. Following this, the properties of virus-like particles loaded with mRNAs, such as stability and stiffness are explored. Then, cell uptake and cargo release, transfection, and translation efficiency of the virus-like particles and lipid nanoparticles are systemically explored. Also, we investigate and compare immunogenicity between lipid nanoparticles encapsulating an immune adjuvant and virus-like particles, intending to enhance the immune response in cancer treatment.

Molecular Design and Stability Study of Self-assembled Chimeric Protein Nanoparticle Vaccine

Primary investigator:

Ms Hong Luo
hong.luo@adelaide.edu.au
Ms Hong Luo's Researcher Profile

Project abstract:

Self-assembled protein carrier vaccines are considered a safe and effective type of vaccine, however, it is found in research practice that the inserted heterologous epitopes would often have a great impact on the assembly, stability, and other properties of the chimeric proteins, leading to failure in designing or difficulties in the downstream process. This study aims to conduct in-depth investigations on the influence of epitopes and insertion sites on chimeric proteins by experiments and molecular dynamics simulations (MDS), to guide more efficient and successful design of self-assembled protein carrier vaccines.

Next-generation biomanufacturing: yeast-based continuous production of low-cost single-domain antibodies

Primary investigator:

Mr Yannis Karavias
yannis.karavias@adelaide.edu.au
Mr Yannis Karavias' Researcher Profile

Project abstract:

Biopharmaceuticals are continuously increasing their share of the pharmaceutical market. They can target difficult emerging diseases like cancer specifically. The downside is the tremendous cost associated with biopharmaceuticals like monoclonal antibodies. Changing from batch-wise production to continuous manufacturing can lower production costs significantly. However, continuous processing has mainly focused on mammalian cell cultures. Next-generation biomanufacturing using alternative hosts offers additional cost savings. Therefore, yeast cells are back in focus, due to their favourable characteristics for cost-efficient manufacturing. In this project, a continuous platform process with yeast cells is developed to produce single-domain antibodies as an alternative to mammalian production processes.

Polysaccharide-based double-grid structure pore-size-adjustable materials

Primary investigator:

Ms Manuella Cazelato Pires
manuella.cazelatopires@adelaide.edu.au
Ms Manuella Cazelato Pires' Researcher Profile

Project abstract:

Developing novel copolymers with double grid / complex lattice structures is the frontier of research direction in materials science today. The aim is to develop various high-performance functional materials based on accessible materials such as polysaccharides, and filamentous proteins, as well as efficient and low-cost solutions to critical problems that are being addressed by industry today, such as low-cost protein purification, and screening of high-value minerals (like lithium and industrial gases). Will also allow the development of cutting-edge high-performance materials for purification purposes, as well as have access to the development of other ultra-high-strength organic materials. The expression of various proteins from functional enzymes to small peptides, from laboratory reaction scale to industrial pilot production scale, will be applied post a purification method designed.

Investigating mechanistic and structural requirements for the formation of unwanted byproducts during in-vitro transcription

Primary investigator:

Ms Cinderella Nowak
cinderella.nowak@adelaide.edu.au
Ms Cinderella Nowak's Researcher Profile

Project abstract:

mRNA technology has come into focus as a promising alternative to conventional therapies, such as vaccines against infectious diseases but also against various types of cancer.
However, there are also challenges mRNA manufacturing must overcome, particularly impurities, such as immunogenic mRNA byproducts, which cause side-effects in the patient’s body and pose a time- and cost-intensive challenge for downstream processes. 
These byproducts are formed by the T7 RNA polymerase, an enzyme that synthesizes mRNA during the mRNA production phase, the in-vitro transcription. After all, the exact mechanisms of how and why they are being formed are not yet well understood. 
Therefore, an optimized manufacturing process is necessary that results in the best possible mRNA quality to ensure the highest levels of safety and efficiency, as fast and less costly as 
possible.

This is what this project aims to achieve. By using different molecular biological and chromatographical methods the requirements for the formation of these byproducts should be fully understood. In addition, the analytical approaches for detecting mRNA impurities should be optimized so that their formation can be monitored in real-time.

Integrated Small-Scale Manufacturing of mRNA therapeutics

Primary investigator:

Mr Federico Moreno Sibaja
federico.morenosibaja@adelaide.edu.au
Mr Federico Moreno Sibaja's Researcher Profile

Project abstract:

Recently, mRNA-based therapies and vaccines have been revolutionizing the pharmaceutical industry by providing unprecedented opportunities for the replacement of conventional therapies, due to features such as rapid vaccine development and precision medicine applications. However, there are several manufacturing challenges in the downstream processing, mainly mRNA instability and impurities, such as byproducts generated during In vitro transcription reaction, which are major bottlenecks for purification strategies. Therefore, effective, highly selective and rapid purification is required. Though chromatography is currently employed for mRNA purification, it faces challenges due to properties similarities between mRNA and nucleic acid byproducts. The aim of this work is the design, development, and optimization of chromatographic chips for mRNA therapeutics manufacturing.