Gene therapies have offered unprecedented potential for treating diseases for which there was thought to be no cure. In this context, viruses have not been the enemy but rather powerful allies, precisely delivering therapeutic genes into target cells.
Despite their contribution, genetic therapies based on viral vectors remain highly expensive and present other associated limitations holding them back. This paves the way for non-viral vehicle alternatives, such as lipid nanoparticles. Cormac Sheridan reflects on it in a recently published article in Nature Biotechnology.
Why must gene therapies go virus-free?
Adeno-associated virus (AAV) and lentivirus are in the race to gain regulatory approval, but their exhaustive analysis in several clinical trials has unveiled some limitations:
- High amounts of biomass are required to produce AAV at high doses, which involves high production costs.
- Their packing capacity is limited to 4.7 kilobases.
- Virus-based vectors present poor-tissue selectivity.
- They are associated with liver toxicity risk.
- They may be immunogenic, generating an immune response in the host after the second dose.
- They may be oncogenic due to chromosomal integration and insertional mutagenesis, especially for lentiviral vectors.
- There is a theoretical risk of replication-competent viruses emerging from recombination events during lentiviral production.
Are there non-viral technology alternatives?
Non-viral alternatives exist, and diverse companies are investing millions to bring these virus-free technologies into reality. Among them are DNA-based nanocarriers, polymer-based nanoparticles, protein-based nanoparticles built from phage proteins or proteins in the body, lipid nanoparticles (LNPs), and other lipid-based nanosystems. Although LNPs have been researched for years, the COVID-19 pandemic raised them to stardom thanks to the development of mRNA vaccines.
Virus-free alternatives must meet some requirements to replace the actual viral technologies. Besides fitting large amounts of content, their production costs should be affordable for therapy access. It would also be crucial to precisely deliver them to targeted organs and tissues.
Controlling the protein corona composition may deliver therapeutic molecules to different organs. Lipid nanosystems are great candidates to replace viral vehicles because they offer unique functionalities that allow for precise manipulation of the protein corona. They can be decorated with a wide range of proteins and specifically engineered to mimic the surface properties of target cells or tissues.
The conception of a single dose in gene therapy is changing. Transgene expression faints over time, calling for redosing. Lack of immunogenicity is a must to overcome one of the main drawbacks of viral vectors. Lipid nanosystems mRNA delivery has already demonstrated that it is attainable to inoculate repeat doses without compromising patients’ safety due to immune responses generated by the delivery vehicle. Also, billions of doses with affordable prices have been manufactured and delivered in record-breaking speed.
LNPs and other types of lipid nanosystems offer a safe, affordable, tunable, and non-immunogenic alternative to viral vehicles.
At DIVERSA, we make it easy for gene therapies to go virus-free. We have developed versatile lipid nanoemulsions that carry many molecules, including mRNA, DNA/plasmid DNA, and proteins.
Our nanoemulsions are bio-inspired, ensuring safety and optimal biocompatibility. Without the need for specialized instrumentation, our technology minimizes material loss due to its high association efficiency. Whether you work with small or large mRNA and DNA sizes or prefer to deliver proteins directly, at DIVERSA, we have a solution for them all. DIVERSA lipid nanoemulsions allow the modulation of their surface properties upon decoration with proteins or other ligands. Additionally, there is a fluorescent option available to guarantee visibility and control.
If you require formulations to suit your project, DIVERSA technology is easily scalable and replicable, increasing the potential for translating your product to the clinic.
We want to help you with your project. Let’s join forces to make lipid nanosystems the real delivery alternative to viral vectors. Contact us to revolutionize your research!
