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Publication Number
US-12029821-B2
Publication Date
2024-07-09
Expiration Date
Abstract
Vesicles, including exosomes, having a coating of a hydrophilic, neutral polymer such as PEG have an increased ability to form a suspension or colloid compared to uncoated vesicles. This enables the coated vesicles to be used to form aerosol droplets such that a liquid formulation containing vesicles can be used in a nebulizer for inhaled administration thereof. Such coated vesicles are also able to pass through mucus and can deliver their cargo into lung cells. Exosomes from mesenchymal stem cells can deliver additional proteins, miRs, mRNAs and other nucleic acid sequences to lung cells providing a regenerative gene therapy for CF, COPD lung cancer and other lung diseases.
Core Innovation
The invention relates to an aerosolizable composition comprising exosomes from mesenchymal stem cells (MSCs). The exosomes have a surface coating comprising a hydrophilic polymer that comprises polyethylene glycol (PEG), and the PEG-based hydrophilic polymer forms a stable aqueous suspension/colloid suitable for nebulized inhalation.
The exosomes carry a cargo comprising microRNA (miR), an anti-miR, an mRNA, a long non-coding RNA, a circular RNA, a small interfering RNA, a short hairpin RNA, a piwi-interacting RNA, a CRISPR RNA sequence, a protein, a cytokine, or a lipid. The polymer has a molecular weight of less than 5 kDa, and the surface coating covers at least 65% of the exosomes’ surface while substantially neutralising the surface charge of the exosomes.
The PEG coating is described as reducing aggregation/agglomeration and improving suitability for aerosolization. The PEGylated exosomes are described as enabling mucus penetration and intracellular delivery in lung cell models, and the disclosed approach is discussed in connection with cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and lung cancer.
Claims Coverage
The document contains one independent claim. The independent claim defines an aerosolizable exosome composition with a PEG-based hydrophilic polymer surface coating, specified surface coverage, substantially neutralised surface charge, and a defined cargo set including multiple nucleic acids, proteins, cytokines, or lipids.
Aerosolizable MSC-derived exosomes with PEG hydrophilic surface coating
An aerosolizable composition comprising exosomes from mesenchymal stem cells (MSCs), wherein the exosomes have a surface coating comprising a hydrophilic polymer that comprises polyethylene glycol (PEG).
High surface coverage of PEG coating
The surface coating covers at least 65% of the exosomes' surface.
Substantially neutralised exosome surface charge
The surface coating substantially neutralises the surface charge of the exosomes.
Low molecular weight PEG hydrophilic polymer
The polymer has a molecular weight of less than 5 kDa.
Exosome cargo comprising nucleic acids and biomolecules
The exosomes carry a cargo comprising a microRNA (miR), an anti-miR, an mRNA, a long non-coding RNA, a circular RNA, a small interfering RNA, a short hairpin RNA, a piwi-interacting RNA, a CRISPR RNA sequence, a protein, a cytokine, or a lipid.
Overall, the claim coverage centers on PEGylated MSC-derived exosomes configured for aerosolizable delivery, using a hydrophilic PEG polymer of molecular weight less than 5 kDa that covers at least 65% of the exosome surface and substantially neutralises surface charge, while carrying a broad cargo set including miRs, anti-miRs, mRNA, and other RNA species as well as protein, cytokine, or lipid.
Stated Advantages
Improves suitability for aerosolization.
Enables mucus penetration.
Provides intracellular delivery in lung cell models.
Reduces aggregation/agglomeration.
Improves targeting of lung diseases including cystic fibrosis (CF), COPD, and lung cancer.
Documented Applications
Use in lung cell models, including cystic fibrosis (CF) air-liquid-interface (ALI) cultures, for mucus penetration and uptake of the PEGylated exosomes.
Potential application to lung diseases including cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and lung cancer.
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