Targeted Exosomes Using RBD-VSVG Fusion for Lung Delivery
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Solution Overview
Problem
Current treatments for COVID-19 lack a targeted delivery mechanism for anti-viral medicines, as most intravenously injected exosomes are absorbed by the liver, failing to specifically target SARS-CoV-2 infected tissues and organs.
Innovation Solution
Development of targeted exosomes based on the RBD region of the SARS-CoV-2 S protein, where a RBD-VSVG fusion protein is expressed, allowing for tissue-specific delivery of anti-SARS-CoV-2 medicines by replacing the extracellular region of VSVG with the RBD of the SARS-CoV-2 spike protein, and a method involving PCR amplification, vector ligation, and ultracentrifugation to isolate and prepare these exosomes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If exosomes are modified for targeted treatment, then delivery specificity to SARS-CoV-2 infected tissues is improved, but manufacturing complexity increases
Solution Approach 1:
The exosome surface is modified with RBD-VSVG fusion protein to create localized targeting capability. The extracellular region of VSVG is replaced with SARS-CoV-2 RBD, creating a specific binding interface that localizes exosome action to ACE2-expressing cells while maintaining the exosome's natural delivery function.
Solution Approach 2:
The RBD-VSVG fusion protein acts as an intermediary between the exosome carrier and the target cells. It mediates the interaction by binding to ACE2 receptors on the cell surface, facilitating targeted delivery of therapeutic cargo to SARS-CoV-2 infected tissues.
2Ease of operation
If intravenous injection of exosomes is used, then treatment accessibility is improved, but liver absorption increases causing loss of therapeutic efficacy
Solution Approach 1:
The invention converts the natural liver absorption pathway into a beneficial targeting mechanism. By incorporating RBD that binds to ACE2, the exosomes are redirected from non-specific liver uptake to specific SARS-CoV-2 infected tissue accumulation, transforming the potential harm of liver absorption into selective tissue targeting.
Solution Approach 2:
The surface properties of the exosomes are changed by incorporating RBD-VSVG fusion protein. This parameter change in surface composition alters the biodistribution characteristics, enabling the exosomes to escape non-specific liver uptake and achieve targeted accumulation in ACE2-expressing tissues.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The targeted exosomes efficiently deliver anti-SARS-CoV-2 siRNA, significantly inhibiting virus replication in mouse lung tissue and alleviating pneumonia symptoms, demonstrating precise and effective treatment for COVID-19.
Implementation Method 1
the entry of that virus into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S) which specifically recognizes ACE2
Implementation Method 2
exosome can deliver specific functional biomolecules (such as a nucleic acid, including a plasmid DNA and a small interfering RNA, an antibody, and a small molecule drug) to recipient cells
Implementation Method 3
ultracentrifuging at 80,000-120,000 g for 60-80 min and collecting the precipitation
Data Source
AI summary
The present invention discloses a targeted exosome based on the RBD region of SARS-CoV-2 S protein and a preparation method thereof. An RBD-VSVG fusion protein is expressed on the targeted exosome of the present invention, and the RBD-VSVG fusion protein is obtained by replacing the extracellular region of VSVG with the RBD of the SARS-CoV-2 S protein. In the present invention, a targeted exosome capable of efficiently and tissue-specifically delivering a potential anti-SARS-CoV-2 medicine is constructed. The targeted exosome is used to encapsulate SARS-CoV-2 siRNA, to specifically inhibit the virus replication in tissues and organs. In a mouse animal model, tail vein injection of exosome encapsulated SARS-CoV-2 siRNA significantly inhibits virus replication in mouse lung tissue and alleviates symptoms such as pneumonia caused by virus infection.