Drugs of the future: Swiss army knives in pill form

Researchers at Aarhus University are developing a new method for making multifunctional drugs that can be assembled quickly and inexpensively according to the needs of the individual patient

2018.03.27 | Peter F. Gammelby

The concept of a multifunctional drug resembles that of the Swiss army knives, which are available in many different versions according to the needs of the users. Foto: Andrew Toskin / CC BY-SA 2.0

A graphical representation of a new multifunctional drug: the gray mesh represents the platform of DNA strand mounted with drug molecules (red), an isotope for illumination (orange), targeting ligand molecules (blue), self-penetrating peptides (purple) and albumin binders for transport (green). Grafics: Kurt V. Gothelf.

Professor Kurt V. Gothelf heads the new Centre for Multifunctional Biomolecular Drug Design. Photo: Lars Svankjær.

Imagine a drug consisting of biological molecules, each of which is constructed to travel in the bloodstream to find and attach to e.g. specific types of cancer cells in a patient. And which subsequently can activate a tracer that will allow the doctors to locate the cancer.

On top of that, the drug can alert the immune system of the patient or penetrate the cancer cell and release a toxin that kills it (the cancer cell, that is).

Now imagine that each of these functions:

- travelling through the bloodstreams by binding to the transport protein albumin

- carrying a drug

- finding and attaching to a carefully defined cell through a ligand molecule

- carrying an isotope that will emit light when present at its final location

- activating the immune system with an antibody

- penetrating barriers such as cell walls by using self-penetrating peptides

- avoiding being attacked by the patient's immune system before reaching its destination    

can be manufactured in advance and be stored in a library of nanoscale biological modules, which can be assembled like tools in a Swiss army knife according to the needs of the individual patient.

Unlike a real Swiss army knife, this one is not made of steel. It consists of a small string of tailor-made nucleic acids (DNA or RNA) that the individual modules attach themselves to by way of different chemical processes.

It sounds difficult, and it is. Bioconjugation – creating stable chemical bonds between biological molecules that do not naturally bind to each other – is a relatively new research field.

Big plans with small modules

Nevertheless, this is the aim of the new Centre for Multifunctional Biomolecular Drug Design (CEMBID) that opens at Aarhus University this week:

To develop new and effective methods for bioconjugation, to design the biological molecules as modules, and to assemble and test the new multifunctional drugs in laboratory experiments.

The centre will focus on two of the diseases that affect humans the most: cancer and arteriosclerosis.

“Our system of using DNA to create personalised medicine is ideal. We are developing new methods to assemble the building blocks that best suit the needs of the individual patient, in a much simpler way than has been possible so far. The aim is to pave the way for a new generation of inexpensive and effective multifunctional drugs,” says the leader of CEMBID, Professor Kurt V. Gothelf from Aarhus University.

He expects that he and his colleagues will have the first multifunctional drugs ready for clinical imaging treatments (such as binding to plaques in constricted veins and emitting light to facilitate scanning imaging or endoscopies) already within six years.

… after 10 years of nerdery

Kurt Gothelf’s own expertise is to program DNA to detain certain proteins and to attach DNA to proteins – something that does not normally occur in nature.

As head of a basic research centre, Centre for DNA Nanotechnology (CDNA), during the last 10 years, he has been working with the programming of DNA strings to assemble two- and three-dimensional nanostructures, which is known as DNA origami. One of the scientists associated with the CDNA was Professor Jørgen Kjems, who now leads one of the groups in CEMBID.

“We have been researching and working with DNA technology for 10 years without knowing precisely which applications it might lead to. Now it turns out to have the potential to develop the multifunctional drugs of the future,” says Kurt Gothelf.

A good investment

The Dean of Science and Technology at Aarhus University, Niels Christian Nielsen, believes that the new research centre is yet another proof that money on free basic research is well spent.

“Basic research with an open and curious mind creates the knowledge that applied science builds upon. CEMBID is a brilliant example of this – it builds on the knowledge gained at the Centre for DNA-Nanotechnology that was founded in 2007 with support from the Danish National Research Foundation,” says Niels Chr. Nielsen.

CEMBID is funded with 60 million DKK from the Novo Nordisk Foundation Challenge Programme.

In addition to Kurt Gothelf and Jørgen Kjems, Associate Professor Ken Howard from Aarhus University and Professor Tony LaHoutte from Vrije Universiteit in Brussels will be principal investigators of the new centre. Ken Howard is an expert in drug delivery and pharmacokinetics, and Tony LaHoutte is highly experienced in clinical investigation of bioconjugates.

 


CEMBID opens officially on Monday March 19.

Read the programme for the opening here.

CEMBID's home page. 

 

Contact: 

Professor Kurt V. Gothelf
iNANO and Department of Chemistry
Aarhus University
Email:kvg@chem.au.dk
Mobile: +45 6020 2725  

 

 

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