RNA and DNA medicines can target any gene or protein in the body. Therefore, nucleic acid-based therapeutics have the potential to treat diseases caused by genetic mutations including diseases that cannot be treated by conventional drugs such as small molecules and biologics.
Challenges with nucleic acid delivery
Naked nucleic acids can cause a strong immune response and are quickly degraded by enzymes in the bloodstream and the gut. Therefore, RNA and DNA medicines must be delivered to target cells using a vector. Viral vectors and lipid-mediated delivery systems are the two main approaches used in RNA therapeutic development.
Viral vectors and existing lipid vector technology can cause liver damage and activate an adverse immune response in human patients. Viral vectors may cause accidental mutations in host DNA, which can lead to cancer. Patients treated with viral vectors can also develop antibodies against these vectors that make the treatment less effective over time. There is clearly a need for improved delivery vehicles before RNA medical therapies can become mainstream.
The LUNAR solution
To address these delivery problems and to improve the safety and tolerance of RNA and DNA medicines, we have developed a novel lipid-mediated delivery system called Lipid-enabled and Unlocked Nucleomonomer Agent modified RNA (LUNAR).
LUNAR works by encapsulating therapeutic nucleic acids and safely delivering them to target cells through a process called endocytosis. The LUNAR particles fuse to target cell membranes and enter the cell where they deliver the RNA or DNA payload. The cell then uses the RNA or DNA medicine to address the disease-causing genetic defect and to produce normal, healthy protein.
LUNAR lipids can be used to deliver very small RNAs such as siRNAs and microRNAs and also larger mRNAs and gene editing technologies such as CRISPR and TALENs. Unlike other lipid-mediated delivery systems, LUNAR can deliver nucleic acids to a range of clinically important cells and tissues. LUNAR lipids are pH-sensitive and biodegradable, causing minimal lipid accumulation in cells after multiple dosing. First-generation LUNAR formulations show a wide therapeutic index in preclinical studies. This means we only need to deliver a small amount of the active pharmaceutical ingredient in order to see therapeutic effects, and so are able to avoid adverse events and side effects.
Benefits of LUNAR
- LUNAR delivery technology can be used with multiple types of nucleic acid therapeutics.
- LUNAR can be administered by multiple routes (IV, IM, nebulized, subretinal, and intravitreal).
- LUNAR can target multiple different clinically important cells including stellate cells, hepatocytes, lung epithelial cells, eye cells, and myocytes.
- LUNAR can deliver mixtures of different RNAs as one drug product.
- Preclinical studies show that LUNAR compounds, unlike other LNP vectors, have a wide therapeutic index.
- LUNAR lipids are optimized for high RNA and DNA encapsulation efficiency, which is important for the cost of manufacturing.
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