Updated: Jul 24, 2021
Using mRNA as a medicine is a radically different approach than treating disease with other drug classes.
mRNA is the set of instructions by which cells make all proteins and send them to various parts of the body. mRNA medicines utilise the advantage of normal biological processes to express proteins and create a desired therapeutic effect. This enables the potential treatment of a broad spectrum of diseases, many of which cannot be addressed with current technologies.
mRNA has the potential to transform how medicines are discovered, developed, and manufactured – at a breadth, speed and scale that will fundamentally change biotechnology and medicine.
Biotech companies Moderna and BioNTech use mRNA technology to produce vaccines effective against Covid-19 with miraculous speed. That has pushed the combined worth of companies in this accelerating field to more than $120 billion.
The COVID-19 mRNA vaccines give instructions for our cells to make a small and harmless piece of what is called the “spike protein.” The spike protein is found on the surface of the virus that causes COVID-19.
COVID-19 mRNA vaccines are given in the upper arm muscle. Once the instructions (mRNA) are inside the immune cells, the cells use them to make the protein piece. After the protein piece is made, the cell breaks down the instructions and gets rid of them.
Next, the cell displays the protein piece on its surface. Our immune systems recognize that the protein doesn’t belong there and begin building an immune response and making antibodies, like what happens in natural infection against COVID-19.
At the end of the process, our bodies have learned how to protect against future infection. The benefit of mRNA vaccines, like all vaccines, is those vaccinated gain this protection without ever having to risk the serious consequences of getting sick with COVID-19.
Rather than growing vaccines in bioreactors, a new generation of biotechnology companies designs instructions so the human body can produce its own therapy.
These novel vaccines exploit the process by which cells build proteins from the information encoded in a single-stranded molecule called messenger RNA (mRNA).
Once the COVID-19 vaccine enters a cell, the mRNA molecule tells it exactly how to build a piece of the SARS-19-CoV virus. Through exposure to the body this virus induces its immune system to mount a response, thereby training the body to fight the real deal if it gets infected by SARS-CoV-2.
Global fund managers and family offices are equally excited. Two of the largest investments in mRNA are Thomas and Andreas Struengmann. The pair helped BioNTech with around €150 million seed funding in 2008. This was after they sold their generic drug business for around €5.5 billion. This investment increased to around €7 billion in 2020.
For Australian fund manager, Michael Frazis, Moderna represents a platform technology company as he recently told the Australian Financial Review “Moderna is now a platform company..medical science is now data science. This is a process that can be used in many different indications”. Frazis fund is up 110% as at 31 December 2020.
A February 2021 company presentation for BioNtech can be dowloaded here
A March 2021 Moderna presentation can be downloaded here
Improved Genetic treatments
There are significant and extraordinary developments in genome sequencing and genetic engineering that will transform all biological enterprises, especially healthcare, and create new ones, like the electronic revolution.
The extraordinary advances in DNA sequencing are leading to an avalanche of genomic information. Genetic engineering can now be done with high speed and precision. The pace of change is accelerating, and biological technologies are intersecting with optical technologies, nanotechnologies, advanced computing and artificial intelligence to create possibilities that were, if not beyond imagination, well beyond feasibility just a few years ago.
An example is CRISPR. Otherwise known as "clustered regularly interspaced short palindromic repeats", CRISPR is a novel gene-editing technology that exploits quirks in bacteria immunity to edit genes in other organisims.
The new technology has spurred dozens of labs around the world into developing the next generation of medical breakthroughs.
Here is a great video explaining CRISPR technology.
Qiagen, founded in Düsseldorf, Germany, are setting about establishing themselves as a global player in the next generation sequencing industry. The company produces sample technologies isolate and process DNA, RNA and proteins from blood, tissue, and other materials. Assay technologies make these biomolecules visible and ready for analysis. Bioinformatics software and knowledge bases interpret data to report relevant, actionable insights. Automation solutions tie these together in seamless and cost-effective workflows.
Gene editing made its first breakthrough in the 1980s, where researchers first succeeded in overwriting defective genes with healthy ones in mice through a process known as homologous recombination.
The technology really evolved when a region of bacterial DNA with an exactly repeating sequence over certain intervals was discovered – CRISPR or Clustered Regularly Interspaced Short Palindromic Repeats. This discovery gave researchers the chance to develop a technique which was simple and effective enough to be used in gene therapy.
CRISPR DNA is an important key to the bacterial immune system and is responsible for fighting off viruses, enabling bacteria to recognize and destroy viruses during future infections. The technology works on three essential components to cleave and destroy viral DNA – the CRISPR-associated CAS genes, the CRISPR RNA (crRNAs) and tracrRNA (trans-activating crRNA). While the CAS9 gene codes for an endonuclease which cuts the DNA, the crRNA serves as a messenger which guides the endonuclease to the location were a cut is needed. There are several pathways of CRISPR activation, one requires a tracrRNA to play a role in the maturation of crRNA.
CRISPR gene editing methods broke all limits of imagination in gene engineering and creates a wide new world of opportunities. Such gene editing tools not only change the way the world looks for cures for genetic disorders, but also impact other practical applications in many areas.
A video explaning QIAGEN technology can be viewed below.
Sophia genetics is an American Swiss biotechnology company with its headquarters in Lausanne and Boston. It provides genomic and radiomic analysis and combines deep expertise in life sciences and medical disciplines with mathematical capabilities in data computing. Their mission is to bring data analytics solutions to market, to support healthcare professionals by maximizing the power of Data-Driven Medicine.
Another example is Antisense Therapeutics Limited (ASX: ANP and FWB: AWY) Antisense technology represents an important breakthrough in disease treatment.
With access to Ionis Pharmaceuticals’ proprietary drug discovery process, Antisense Therapeutics Limited can move quickly from drug discovery into developing therapies. Once a therapeutic application and corresponding gene target has been identified, an antisense lead inhibitor compound can be rationally designed within hours suitable for use in research and clinical trials. This compares with traditional drug discovery approaches which can take years to produce such a lead compound. Antisense drug development also benefits from uniform methods of manufacture, formulation, and delivery of antisense compounds.
Antisense is an innovative platform for drug discovery. Biotech platform technologies combine all the elements that are necessary to rapidly and efficiently create a stream of new products.
A recent company presentation for Antisense can be downloaded below
Synthetic biology and anti-infectives
The ability of antibiotics to cure bacterial infections is at a serious risk due to the emergence and worldwide spread of superbugs.
The World Health Organization notes that antimicrobial resistance one of the greatest global health threats.
Investors are also looking closely a the sector. The Former U.S. Food and Drug Administration (FDA) Commissioner Scott Gottlieb is focused on investing in companies developing new antibiotics. “I’m very interested in finding opportunities in the anti-infective space, particularly around multi-drug resistant organisms,” Gottlieb said in an interview. “Anti-infectives have been unloved for a very long time. There’s a huge clinical need.”
The significant lack of innovation and investment in the development of novel antibiotics and the ever-changing, dynamic nature of infectious disease, has enabled the emergence and spread of drug-resistant pathogens.
According to SynBioBeta, during the first half of 2020, total investment in the sector reached over USD $3 billion - an increase of 60% from 2019. The largest deal was done by Sana Biotechnology (USD 700 million) for therapy development based on enginnering cells.
In Australia there is a global leader working in the area of synthetic anti-infectives. R327 developed by Recce Pharmaceuticals Ltd (ASX: RCE) and (FWB: R9Q) has destroyed every bacterium it has been tested against, including superbugs, and has proved invulnerable to any attempt by bacteria to mutate and overcome its mechanism of action.
The promising new drug is currently in the final preclinical stages with preparations underway for first-in-human clinical trials. Recce’s new compound is a broad-spectrum antibiotic initially to be used intravenously against Escherichia coli and Staphylococcus aureus bacteria in the blood, including superbug forms. In a sign of growing global interest, Australian-based Recce has been awarded qualified infectious disease product (QIDP) designation by the US Food & Drug Administration (FDA).
The QIDP designation, awarded under the Generating Antibiotic Initiatives Now (GAIN) Act, means the antibiotic has fast track designation along with 10 years of market exclusivity post-approval.
“It is a completely new class of broad-spectrum antibiotic that will kill all bacteria, including super-bugs. Even when bacteria attempt to mutate, the antibiotic continues to work,” said CEO, James Graham. Traditionally, antibiotics have come from natural sources, for instance penicillin, or are modified to achieve broad-spectrum activity. Using a so-called ‘lock and key’ mechanism at the cellular level, these drugs lock into a specific part of the bacterial membrane and attack it. Once the bacteria mutate, the antibiotic is rendered useless. The global market for antibiotics is over €35 billiion,
The compound binds to the outer membrane of bacteria, interacts with bacterial plasma membrane proteins causing the bacteria to burst
Based on a patented polymeric structure, Recce’s antibiotic has millions of active sites, compared with only one, two or three active sites of traditional antibiotics.
Recce VP and co-inventor of the technology, Michele Dilizia, said it was widely acknowledged that antimicrobial resistance (AMR) was one of the world’s most urgent unmet medical issues. “Multidrug-resistant bacteria cause the deaths of more than 700,000 people annually, and millions more have serious complications from infections. AMR is forecast to kill up to 10 million people annually by 2050 unless solutions are found,” she said.
Recce is officially the only synthetic antibiotic in development and the only sepsis drug candidate.
A great video on how Recce Pharmaceuticals synthetic anti-infectives work can be viewed below
A recent company presentation for Recce Pharmaceuticals can be downloaded below
A Recent ASX Release highlights the fact that Recce is the only synthetic polymer drug candidate in development for treating Sepsis
Introducing Recce Pharmaceuticals German language presentation from March 2021