With a solid $25 million investment, this Australia-based Institute is delving into RNA therapeutics

By 孙丽娜 Nov. 24th 2022

"The RNA revolution is just getting started." said Professor Pall Thordarson, Director of the UNSW RNA Institute.

In recent years, Pfizer and Moderna have made a fortune and soared in the pharmaceutical industry because of the mRNA vaccine for Covid. It is reported that in 2021, Pfizer provided 2.2 billion doses of mRNA vaccinefor Covid to the world. In the same year, Moderna provided 807 million doses of that. The R&D of mRNA vaccine for Covid has become the hot track of the moment.

In fact, the future of RNA therapeutics is not just vaccine for Covid, and Pfizer and Modena's success with mRNA vaccines is just the tip of the iceberg of the RNA therapeutics technology revolution. In addition to addressing current and future infectious diseases, RNA therapeutics could also treat cancer, genetic and autoimmune diseases.

To catch up with this revolution, Australia, a major biotech R&D center in the Asia-Pacific region, the University of New South Wales (UNSW) is also investing $25 million in 2021 to establish the UNSW RNA Institute, dedicated to the development and production of RNA therapeutics.

It is reported that the institute will conduct preclinical trials for the treatment of COVID-19 and cancer using RNA therapeutics produced in NSW, and in June this year, the pilot scale production of siRNA for RNA-based therapeutics will be put into production.

So how was the UNSW RNA Institute established? How will it translate scientific results in the future? With these questions, VB-Create has interviewed Professor Pall Thordarson, Director of the UNSW RNA Institute, to learn more about the UNSW RNA Institute.


Prof. Pall Thordarson, Director of UNSW RNA Institute

For the convenience of readers, VB-Create has edited the text without changing the original meaning.

Over ten years in the making, 

focusing on three major research areas

VB-Create: Could you please share the founding story of RNA Institute and what role UNSW plays in it?

Prof. Pall Thordarson: The founding story actually goes more than 10 years back because we established here at UNSW more than 10 years ago, a Center for NanoMedicine. And the NanoMedicine Center has a huge focus on delivery systems, included delivery of siRNA for cancer therapeutics. Through that research, I felt that it was clear to methat RNA therapeutics would be a major player in the future.

And I started to put this idea in 2019 to the Chief Scientist Office of our state government here in Sydney and to germinate there with the government. Now as the pandemic went on and with the international success of mRNA vaccines, that proposal should gain momentum. And then in 2021, my university came back to me and said what we think is actually a good idea. We should do something about it and more importantly, our state government with the Premier said the same.

And the Premier set a task for calling us between Chief Scientist Office in there and the state government, and all the universities in New South Wales and other representative universities in the working party to put together initials of RNA ecosystem and manufacturing plan. And just for reference, the state governmenthas already invested over $200 million for the next 10 years into manufacturing, research and development at the state level. This is in addition to the investment from my own university.

At both the University and state-level, we feel that we are in a very good position to lead the world when it comes to applications of RNA in gene therapies and gene medicine. And this comes on the back of co-investment from the State government in the same time into viral vector technologies. A lot of work here in Sydney is around understanding rare diseases and long historical strength in epigenetics research and coupled with NanoMedicine.  

In RNA therapeutics it doesn't matter whether you’re developing mRNA or other different types. It's delivery that is the main challenge. We at the UNSW RNA Institute think what we have here is a very unique collection of expertise across Biology, Medicine, Chemistry, etc. And that's foundation of both the state plan and also of the Institutionformed last year.

VB-Create: What are the criteria for recruiting researchers and students to the Institute (professional orientation, research ability)? What do you value more?

Prof. Pall Thordarson: Scientific excellence is always a key priority. Butwealso want to make sure that there's good complementarity and diversity both in terms of scientific expertise and seniority. Because sometimes you get a really good idea from relatively junior people.

We have a well-esteemed internationally famous people and also some early rising stars. And we got people who work in epigenetics, fundamental biology, doing basic RNA chemistry, working on novel polymer systems with delivery, all the way to microfluidics, novel sensors and into applications of RNA, cancer, in anti-viral spot for HIV and for COVID-19, adding to treatments of rare genetic disorders.

We organized ourselves around 3 themes, RNA chemistry, RNA Biology and RNA medicine. We feel that is our strength but also therefore going to be the key challenges. We want to contribute to our delivery, which is the key challenge. When it comes to delivery systems, thereare a lot of challengesof manufacturing, analysis across the RNA field, sensing with the focus on new methods to measure RNA directly in blood samples, something called liquid biopsy, and finally RNA interactions with proteins in the cell in particular, to understand their many unscripted questions about basic RNA biology. 

And in terms of health areas, we focus on 3 areas at this point. Covid-19 in some ways because of the urgency there, but we're not so much focused on the vaccine and we actually more interested in developing normal siRNA antivirals and those linking to antiviral programsthat have been running here for several years against HIV. Covid is now unfortunately likely to stay with us, so we need antivirals, particularly for people who are immune-compromised. siRNA Therapeutics could be a way to deal with chronic infections and immune-compromised people just as it is for HIV.

Our second focus area is oncology or cancer, with 2 key areas of children's cancers and pancreatic cancer. Third area is the rare and genetic disorders. And we have a pediatrician who treats kids with spinal muscular atrophy. This used to be a lethal genetic disorder but is not treatable and actually one of the treatment is an RNA technology. So we're interested in working with a team of people looking at what other rare Genitive shortage could be treated with our new technologies.

VB-Create: There are so many areas that hasn't been addressed. Why did you even choose those areas in the first place? Why is that?

Prof. Pall Thordarson: In terms of the health areas, we did do it mainly on the back of where our current strengths are. We got a very strong research institutionin infectious diseases that already had a program on COVID-19 and HIV and then potentially oncology. We have another institution that is connected to our institution, which works on children's cancerresearch.

 And as the same we intensified clinical research. In UNSW we have already one of the world's leading clinicians when it comes to developing these treatments again for rare disorders and have been running clinical trials with international companies. 

With RNA accelerator, multiple projects 

are now in animal studies

VB-Create: Could you share about some of the current key research projects you're doing or you are most excited about? How is it progressing right now?

Prof. Pall Thordarson: The first one is this idea of using siRNA as an antiviral families progressing towards animals now. And I believe some of the oncology siRNA programs are a similarity about to cross into animal studies. Now we have also collaborated with people in Sydney outside UNSW working on 9 other types of mRNA vaccines. What we did was to help them with the delivery system and again I think they are starting their animal studies, too. I'm quite proud of all these 3 because we only started making RNA sort of back in April and we are already making material that people are using in animal studies.

VB-Create: How do you work with clinical centers? How are the results?

Prof. Pall Thordarson: The institution itself is more on the size of production and we do have one clinician within the institution. But the institution is part of university and we have connection to those research institutions, which include also large clinical trial units.

And within Sydney, the state government also operates a very effective system to help people setting up clinical trials in Sydney. We would not do that directly; we have the connections to help people to get goals there, both our own people and also international partners.

We are already in discussions with companies from across the world who want to work with us. Thereare a lot of positives when it comes to running clinical trials in Australia and here in Sydney particular. We definitely have all those connections here.

VB-Create: What is the plan after the project is brought to the clinic? Will there be follow-up collaborations? How will it be carried out?

Prof. Pall Thordarson: This links to what the government has planned. It's investing in both the 10 year research plan, which we will probably also be a big part of. But it's also investing in a manufacturing plan, which will be operated by a private company and operators are being selected now. 

That would mean that project coming out of our institution could go to that large GMP factory to have the material made to do the actual clinical trial. And also, if we find the collaborator overseas who wants to do clinical trials and then they can go and have the material made in Sydneyand do clinical trials there.

We're trying to build up the whole value chain here. We got the basic science done in our institution. We got the facility to help people scaling up and then the government is also supporting that work and the translation to clinical trials. Hopefully that will allow us to pave the ground for new companies being function.

We are also very interested in working with companies from other countries and recognition. They may want to do the manufacturing elsewhere but might still want to work with us and do part of the clinical development and trials here.

VB-Create: We noticed that you also got a RNA accelerator. What is the mission or the main task of it? How to achieve that?

Prof. Pall Thordarson: It has 3 main missions. The first one is to provide our researchers and not just actually in UNSW but also other people in Sydney with access to pre-clinical scale material. Because for academic researchers what they would normally do is sort of on a bench scale and it can do the initial test; but there's a gap between that and taking it to a factory. So the accelerator is mainly about pre-clinical pilot production. People can get the material in a large scale with better consistent purity.

Mission number 2 is really to train the workforce. This is a completely new technology and we're going to train people up in that intermediate step. But we can also use the pilot facility to train people up and while I work in the actual factories, including not just in Sydney, but other factories across the world.

And our third purpose is to work with all the hubs and centers and companies around the world to help their own people getting quickly from the bench to the clinic.

VB-Create: Could you share a few examples and your experiences with us?

Prof. Pall Thordarson: We already made a couple of batches that are going into animal trials. So that's our example of working with researchers by developing siRNA treatments for Covid or for cancer and we are making the material for them to take to animal studies.

We also now in a similar way start to work with the Department of Primary Industries helping developing the animal vaccines towards the clinics. so that's on the training program. We haven't gone that far with that because it just started. But we're thinking of setting up postgraduate program and also micro credential short courses were offered companies too if they need to send their people to us for short term training.

And in terms of collaboration with the centers, we have collaborations already with a couple of key crops in Australia, Queensland and Melbourne. And we are sort of slowly setting up more formal relationship with a couple of companies and centers around the world.

Focusing resources to transform results 

and build RNA ecosystem in Sydeney

VB-Create: Do you encourage researchers to start their own business? Or do you transfer the technologies?

Prof. Pall Thordarson: Our university as a whole, not just the institution, is more and more trying to encourage academics to create their own companies. And we have good mechanism in place. Our own institution is already collaborating with SynBio 10x that was set up to help startup companies in a synthetic biology space. We can more effectively to teach people how to create their own companies and we also have a development officer helping with that.

VB-Create: What kind of help and guidance does the RNA Institute provide in the translation of research results? What are the features of your translation model?

Prof. Pall Thordarson: Both the university itself and even State-sponsored scheme will help people there. So we're not trying to replicate everything the university can do already. People can go to the university for specialist advice on how to set up the company structure and that sort of stuff. But within institutions that we recently appointed Mr. Development Officer who has experience from the investment Circles in the US and he can help people with understanding about raising funds. 

More importantly in the early phases, we know that for many of the startups where they can run into problems is that they simply need access to material or a particular instrument. And I think in the first phase, we will try to help people with that, giving the competitive edge that way. 

VB-Create: What advice do you have for the researchers who want to translate their results?

Prof. Pall Thordarson: Obviously many people work directly on developing new mRNA for vaccines or protein replacement and so on. 

But I think what I would also emphasize is that a lot of people don't realize they hold the key technologies that are really important even though they don't work directly with RNA, such as people working on polymer systems that could be used with delivery, people workingon microfluidics to be used for sensing and even improving just the allowances of the materials.  

I come from the chemistry field and there's a lot of analytical chemistry to be undone. There might be people working on what I think has nothing to do with RNA, but actually we think about it for a second, they may have the solutions to solve the problems in the fields. So I think just being open minded if you're interested in this, and take a bit of risk.

VB-Create: What is the long-term strategic plan of RNA Institute? What are the hopes and expectations?

Prof. Pall Thordarson: We are hoping in 10 years time, especially given the strong State government investment, there will be a thriving RNA ecosystem with some companies here in Sydney. That's the larger picture. 

And then for our institution, we like to see it growing from when it's now to having it's own building with maybe 100 researchers. And hopefully by then, some successful RNA companies would have been created from our Institute. 

We have now 20 academic researchers and probably would get up about 50 people, but we're actually not all co-located. We have the facilitiesco-located but next step would be to have a separate building. 

Our core research will focus together and we could start to also help spin-off companies nearby. And I would like to see from that institution in that next 10 years, some one or two truly significant international scientific breakthrough, something that really everyone knows would come from us.