Advanced nanoparticle delivery system for targeted pulmonary administration of therapeutic nucleic acids

Lipid nanoparticles (LNPs) are designed for delivering RNA to lung tissues via inhalation. Composed of ionizable lipids, phospholipids, PEG-lipids, and cholesterol, they encapsulate RNA for therapeutic or immunological purposes, maintaining stability during nebulization.

Background

Gene therapy and editing hold significant promise for treating genetic diseases, particularly those affecting the lungs, such as cystic fibrosis. However, delivering gene therapies at therapeutic concentrations systemically remains a challenge. Direct pulmonary delivery of therapeutics is a more effective approach due to the lungs’ ability to locally deposit treatments. Despite this, there is a pressing need for compositions that can efficiently and safely deliver nucleic acid-based therapeutics to lung tissues.

Existing methods struggle with achieving sufficient therapeutic concentrations, maintaining stability during delivery, and ensuring efficient uptake by target cells. Additionally, the process of nebulization or aerosolization, necessary for pulmonary delivery, often compromises the integrity and efficacy of the therapeutic agents.

These challenges highlight the necessity for innovative delivery systems that can overcome these barriers and enhance the delivery of gene therapies directly to the lungs.

Technology description

Lipid nanoparticles (LNPs) are advanced delivery systems designed to transport biologically active polynucleotides, such as RNA, to specific target tissues, notably the lungs. These nanoparticles consist of ionizable lipids, phospholipids, PEG-lipids, and optionally cholesterol, which work together to encapsulate RNA molecules, including mRNA. The encapsulated mRNA can encode therapeutic proteins or antigens, making these nanoparticles versatile for therapeutic or immunological applications.

The LNPs are optimized for pulmonary delivery, either as aerosols or dry powders, ensuring efficient delivery to the lungs. Key characteristics of LNPs, such as particle size, zeta potential, and encapsulation efficiency, are meticulously controlled by adjusting the molar ratios of their lipid components. Additionally, excipients like sugars or amino acids may be included to enhance stability and delivery efficiency, ensuring the structural integrity and functionality of the LNPs during nebulization.

What differentiates this technology is its ability to efficiently and safely deliver nucleic acid-based therapeutics directly to lung tissues, overcoming the challenges associated with systemic delivery. The LNPs’ design allows for precise control over their physicochemical properties, which is crucial for maintaining stability and functionality during the delivery process.

The use of ionizable lipids facilitates endosomal escape, a critical step for the successful release of the RNA payload into the target cells. Furthermore, the inclusion of PEG-lipids enhances the nanoparticles' stability and circulation time, while the option to include cholesterol improves encapsulation efficiency.

This combination of features makes LNPs a powerful tool for gene therapy and vaccination, offering a promising approach for treating genetic diseases and stimulating immune responses through targeted pulmonary delivery.

Benefits

Efficient delivery of RNA to target tissues, especially the lungs
Potential for gene therapy and editing to treat genetic diseases like cystic fibrosis
Optimized for inhalation as aerosol or dry powder for pulmonary delivery
High encapsulation efficiency and stability during nebulization
Capability to deliver therapeutic proteins or antigens for therapeutic or immunological purposes
Use of excipients like sugars or amino acids to enhance stability and delivery efficiency
Potential for treating lung diseases, injuries, or infections
Ability to stimulate immune response by encoding antigens