According to scientists at Massachusetts Institute of Technology (MIT), scientists have relied on synthetic nanoparticles for gene therapies previously, but the particles can be inefficient.
Many scientists often use viruses for DNA delivery, yet this can be more expensive to produce and can integrate their own DNA into the cell’s genome limiting applicability in genetic therapies.
Jacob Becraft, an MIT graduate student and one of the lead authors of the study, told us that with mRNA scientists can control the location, timing, and intensity of protein expression.
Becraft and his team concluded that, with this technology, gene therapy could be delivered with more precision and each treatment could be more successfully tailored to each patient.
mRNA as a gene therapy driver
Since mRNA carries copies of the information contained in DNA to ribosomes, which in turn assemble proteins, scientists can induce production of the desired protein without having to push genetic material into the cell’s nucleus or genome, such as in DNA-based gene therapy.
Using mRNA, the researchers developed circuits selectively stimulating immune cells to attack tumors, making it possible to target tumor cells that have metastasized to difficult-to-access parts of the body.
Becraft explained, “Our high-throughput assembly method for genetic circuits allowed rapid testing of circuit topologies in order to elucidate design rules which improved performance. This also enabled us to design more advanced systems, such as the small-molecule responsive circuits highlighted in this research.”
Through single strand RNA circuits that include genes necessary for the desired therapeutic proteins these circuits could be “tuned” to allow different proteins to express at different times, from the same strand of RNA.
“These approaches have already shown clinical efficiency, through our platform utilizes genetic circuits to fine tune each aspect to reach maximum efficacy,” Becraft further explained,
mRNA applications in gene therapy
“DNA-based gene therapies have demonstrated curative effects in the clinic via long-lasting expression and are well suited for applications including protein replacement therapies. mRNA is more suitable for application in which transient expression of proteins can induce long-lasting effects such as vaccination or cancer immunotherapy,” said Becraft.
He said that prophylactic vaccines and cancer vaccines are a potential application of mRNA treatments since transient expression is advantageous. mRNA also has modality for applications that require repeated dosing because mRNA can be readily delivered to cells to induce protein expression since it doesn’t have to overcome the ‘nuclear barrier’ the way DNA does.
Becraft and his research team at MIT have branched off and started their own company to further develop this mRNA approach.
In the pharmaceutical industry, mRNA has been the driver behind new manufacturing sites, pipelines, and deals – companies like Sanofi, Pfizer, AstraZeneca, and Moderna have invested in the technology.
The clinical stage immunotherapy company eTheRNA recently invested $6.6 million (€5m) in a current good manufacturing process (cGMP) compliant mRNA manufacturing facility. The facility will allow for the company to increase production on its three mRNA encoding proteins used in immunotherapy.
In 2017 the VP of Sanofi Pasteur Nicholas Jackson spoke at Bioprocessing International (BPI) Europe 2017 stating, in regards to mRNA, “It’s kind of one of those things that you can’t afford to not be involved in because if it is the next platform, it is a complete gamechanger.”
Just a little over a year later, the MIT study expands the possibility that with the right programming mRNA may be the ‘gamechanger’ for gene therapy in pharma.
