Chappell et al. (2024) “Use of HSC targeted LNP to generate a mouse model of lethal α-Thalassemia and treatment via lentiviral gene therapy” Blood.
DOI: 10.1182/blood.2023023349
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RNA vaccines gained global awareness in successfully combating the COVID-19 pandemic. In partnership with BioNTech and Pfizer, the Acuitas team supported the development of the highly effective and safe COMIRNATY® COVID-19 vaccine.
Vaccines, enabled by our lipid nanoparticle (LNP) technology, are currently in clinical development to combat a range of infectious diseases. This includes common infections such as influenza, RSV and shingles. However, the versatility of mRNA technology combined with the payload capabilities of our LNP provides a potential opportunity to protect against infections where conventional vaccines have largely failed. Specifically, mRNA-LNP vaccines can express multiple viral antigens, providing a much broader immune response than some current vaccine technologies. Also, where different strains of infectious organisms are present in different parts of the world, mRNA-LNP vaccines can be geographically tailored to protect against each different strain. Our LNP technology is currently supporting the clinical evaluation of a malaria vaccine and an HIV vaccine.
An important advantage of mRNA vaccines over traditional vaccines is that they can be quickly developed to target new, emerging viral threats, as was first demonstrated for COVID-19. With avian flu and mpox as potential future threats, development of mRNA vaccines against these viruses is ongoing, employing our LNP delivery technology.
Cancer continues to represent the single most challenging disease globally. While there have been advances, options and treatment, effectiveness remains limited. Enrolling the body’s own immune system to fight cancer has been shown, in some cases, to provide important benefits, but more progress is needed. mRNA cancer vaccines express proteins only found in cancer cells to trigger an immune response, leading to immune cells attacking and destroying the cancer cells. We support cancer vaccine development following the two approaches described below.
Some types of cancer express common mutant proteins. Accordingly, cancer vaccines are in clinical development, wherein mRNA is delivered, using our LNP, to express those cancer-specific mutant proteins. In this case, many – if not most – patients with a specific cancer, can be treated with the same vaccine.
As the name implies, these vaccines are created to deliver mRNA expressing the specific cancer neoantigens found in individual patients. In this type of therapy, the patient’s tumour is first biopsied and analyzed to identify specific cancer antigens present in that specific tumour. Individual mRNAs are then generated to express those antigens and delivered to the patient in our LNP to trigger anti-cancer immune responses.
Drugs for individuals with genetic diseases typically treat only the symptoms and not the underlying genetic cause. Emerging new gene editing and gene modulation therapeutics, however, may offer permanent or durable correction of the disease at the genome level. The first clinical proof of concept for a gene editing therapeutic to treat familial hypercholesterolemia was recently reported using a nucleic acid therapeutic enabled by our LNP technology.
A variety of different gene editing methodologies are currently in clinical evaluation. Some are intended to “switch off” genes that are causing disease while other therapeutics aim to correct a genetic defect to allow a gene to function normally. Our LNP technology is supporting our partners in advancing gene editing therapeutics to treat serious diseases.
Unlike gene editing therapeutics, which make a permanent change (edit) to the genome, gene modulation therapeutics act through an epigenetic mechanism. This can durably “switch on” or “off” certain genes or gene clusters to address a genetic disease. Our LNP technology is supporting clinical stage programs in various indications, including cancer.
Monoclonal antibodies have important clinical applications in the treatment of a range of diseases, including autoimmune diseases and cancer. The application of mRNA technology to express monoclonal antibodies offers significant potential advantages to currently approved antibody therapeutics. First, the versatility of mRNA technology allows for the design and expression of complex monoclonals much more efficiently and rapidly than conventional approaches. Second, having the monoclonal antibody generated by the patient avoids the challenging and expensive manufacturing processes typically required to prepare the recombinant protein.
Our LNP technology is currently supporting the clinical development of mRNA monoclonal antibodies to treat cancer.