Targeted extracellular vesicles for delivery of therapeutics
Inventors
Sayre, Richard • Vinogradova-Shah, Tatiana • Pertzev, Alexander
Assignees
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Publication Number
US-12180481-B2
Publication Date
2024-12-31
Expiration Date
Abstract
The present invention is directed to Saccharomyces-generated extracellular vesicles (EVs) comprising a foreign RNA molecule or protein and at least one foreign membrane surface exposed ligand that specifically binds to a target receptor displayed on a target cell. The present invention also relates to methods of making and using these Saccharomyces-generated EVs for targeted gene silencing. The present invention also relates to fusion proteins comprising a Saccharomyces extracellular vesicle anchor protein and a second peptide designed to bind to cell-specific receptors.
Core Innovation
The invention describes a pharmaceutical composition for the treatment of SARS-COV-2 that includes extracellular vesicles (EVs) containing a heterologous ribonucleic acid (RNA) molecule directed to inhibit the expression of a SARS-CoV-2 gene, together with a pharmaceutically acceptable carrier. The EVs are generated from Saccharomyces boulardii, and the EV-associated heterologous RNA is characterized by defined RNA classes and sequence or homology constraints.
The invention further specifies that EVs can include, optionally, at least one heterologous membrane surface ligand that binds to a target surface molecule displayed on a target cell. The heterologous membrane surface ligand is linked to an anchor protein embedded in the lipid bilayer of the EV, and the targeting framework includes ACE2, NRP1, and TMPRSS2 as target surface molecules and angiotensin II and VEGF-A as membrane surface ligands.
The invention also provides that the heterologous RNA can be a dsRNA, miRNA, or siRNA directed to inhibit expression of a pathogen gene or an endogenous gene of a target cell. The EV and RNA design is presented as enabling targeted gene silencing through EVs generated from Saccharomyces boulardii carrying heterologous RNA and, when included, heterologous membrane surface ligands for receptor-directed binding.
Claims Coverage
The independent claim set includes three independent claim families. Across these independent claims, the core inventive coverage includes EVs generated from Saccharomyces boulardii that contain heterologous RNA directed to inhibit gene expression, optionally combined with heterologous membrane surface ligands linked to an EV lipid bilayer-embedded anchor protein for binding to target cell surface molecules.
SARS-CoV-2 EV RNA pharmaceutical composition from Saccharomyces boulardii
A pharmaceutical composition for the treatment of SARS-COV-2 comprising a quantity of extracellular vesicles (EVs) containing a heterologous ribonucleic acid (RNA) molecules directed to inhibit the expression of a SARS-CoV-2 gene, and a pharmaceutically acceptable carrier, wherein the EVs are generated from Saccharomyces boulardii.
Pathogen or target-cell gene inhibition using Saccharomyces boulardii EV heterologous RNA composition
A pharmaceutical composition comprising a quantity of extracellular vesicle (EVs) containing a heterologous RNA directed to inhibit the expression of a pathogen gene, or an endogenous gene of a target cell, and a pharmaceutically acceptable carrier, wherein the EVs are generated from Saccharomyces boulardii.
Ligand/anchor linked EV carrying heterologous RNA generated from Saccharomyces boulardii
An extracellular vesicle (EV) comprising a heterologous RNA molecule and optionally at least one heterologous membrane surface ligand that binds to a target surface molecule displayed on a target cell, wherein the at least one heterologous membrane surface ligand is linked to an anchor protein embedded in the lipid bilayer of the EV, and wherein the EV is generated from Saccharomyces boulardii.
The independent claims collectively cover pharmaceutical compositions and EVs generated from Saccharomyces boulardii that contain heterologous RNA directed to inhibit expression of a SARS-CoV-2 gene or another pathogen/target-cell gene, and an optional EV surface targeting mechanism where heterologous membrane surface ligands bind target cell surface molecules via an anchor protein embedded in the EV lipid bilayer.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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