Messenger RNA (mRNA) can be used as protein replacement therapy to treat diseases caused by a lack of protein, or by defective proteins, such as cystic fibrosis. If a gene has a mutation that stops it from producing protein or causes it to produce defective protein, mRNA medicine can provide a healthy version of the missing protein.
We have a number of mRNA medicine development programs that leverage our proprietary LUNAR delivery system and mRNA design and production capabilities. We have a partnership with Cystic Fibrosis Foundation Therapeutics, Inc. to develop novel mRNA therapeutic candidates to treat cystic fibrosis and a strategic collaboration with CureVac AG to jointly discover, develop and commercialize mRNA therapeutic candidates to treat ornithine transcarbamylase (OTC) deficiency and other diseases. We have also partnered with Ultragenyx to develop up to ten mRNA therapeutic candidates for rare disease targets. The first disclosed indication is Glycogen Storage Disease type III.
siRNA, miRNA, and ASO
RNA interference (RNAi) is a natural mechanism used by the body to turn off genes without permanently changing DNA, and it controls how and when genes are turned into proteins. RNAi occurs when a small RNA, such as small interfering RNA, antisense RNA or microRNA, binds to messenger RNA (mRNA) and stops a cell from turning that mRNA into a protein product.
Small interfering RNA (siRNA) and antisense oligonucleotides (ASO) can precisely bind to one messenger RNA (mRNA) and tell machinery in the cell to destroy that mRNA. These mechanisms can be used to prevent mutated genes from being translated into defective disease-causing proteins.
MicroRNAs are small RNAs that naturally occur in humans and regulate how much protein is made from messenger RNA (mRNA). Each microRNA can target hundreds of different mRNAs and so can regulate entire networks of genes. Unlike other small RNAs, microRNAs can also work to increase the amount of protein made from mRNA. This means that microRNA medicines can be used to treat diseases like cancer that have too much of some proteins but too little of others.
Our LUNAR lipid-mediated delivery system and UNA oligomer technology can be used to make safer, more effective RNAi-based medicines. RNA medicines can stimulate an adverse immune response, and our LUNAR technology can prevent this by delivering the siRNA, ASO, or microRNA directly into target cells. In addition, siRNA medicines can sometimes bind imperfectly to unintended mRNA targets. Adding UNA into the siRNA sequence can prevent these off-target side effects.
CRISPR, TALEN, and meganucleases
Human DNA has roughly 20,000 genes. Each gene contains the code needed to make one or more proteins. In some cases, when a gene contains a mutation, the body makes too much or too little of the corresponding protein, or makes defective versions of the protein. Many diseases, including Huntington’s disease, cystic fibrosis and cancer, are caused by DNA mutations.
It is now possible to edit genes to remove disease-causing mutations. Gene editing is one of the newest classes of medicines and holds the promise of removing the genetic causes of cancer, cardiovascular diseases, neurodegenerative diseases and rare diseases. Gene editing medicines may also be effective against infectious organisms.
Gene editing tools (such as CRISPR, TALEN, and meganucleases) use a mixture of enzymes, RNA and DNA to cut out mutated DNA and replace it with a healthy sequence. This treats the genetic cause of disease.
RNA, DNA and enzymes are rapidly degraded in the gut and in the blood stream. Arcturus’ proprietary LUNAR technology can be used to deliver gene editing tools directly into target cells where they can edit out disease-causing mutations. Arcturus’ UNA oligomer chemistry can also be incorporated into guide RNA strands. used in CRISPR gene-editing approaches, to reduce off-target effects.
Replicon RNA and DNA
RNA-based vaccines are a potential new class of RNA medicines. RNA vaccines can be developed more rapidly than traditional vaccines in response to infectious disease outbreaks. Unlike traditional vaccines, RNA vaccines can also be effective in infected patients. Therefore, these vaccines can be therapeutic as well as prophylactic.
RNA vaccines can be generated using either messenger RNA (mRNA) or self-amplifying RNA. Both mRNA vaccines and self-amplifying RNA vaccines provide genetic instructions to the body’s own cells to unleash a potent immune response against infectious organisms. Typically, self-amplifying RNA vaccines require lower doses than mRNA vaccines because they can reproduce themselves inside immune cells.
DNA vaccines are also a promising approach to treating cancer. DNA vaccines contain small sequences of DNA from tumor cells. This stimulates the patient’s own immune system to fight the cancer. DNA vaccines are also an effective way of immunizing against infectious diseases. These vaccines can prime the immune system to protect against infectious diseases without exposing patients to potentially harmful pathogens.
One of the major obstacles in vaccine development is delivering the DNA or RNA to immune cells. Naked DNA or RNA is rapidly degraded in the gut and bloodstream. We are using our proprietary LUNAR lipid-mediated delivery system, in partnership with Synthetic Genomics, to develop self-amplifying RNA-based vaccines and therapeutics for both humans and animals. Arcturus is also exploring potential of LUNAR to enable mRNA and DNA-based vaccines.