Dual-Omics Approach Unveils Novel Perspective on the Quality Control of Genetically Engineered Exosomes

Area of Science:

• Biotechnology
• Nanomedicine
• Molecular Biology

Background:

• Exosomes are promising for targeted drug delivery but face quality control challenges due to inherent diversity and genetic modifications.
• Ensuring the quality and safety of engineered exosomes is critical for their successful clinical translation.

Purpose of the Study:

• To develop and validate a dual-omics framework for comprehensive quality assessment of genetically engineered exosomes.
• To compare the transcriptomic and proteomic profiles of engineered exosomes with control samples.

Main Methods:

• Generation of genetically engineered exosomes using gene fusion and transfection in human 293T cells.
• Dual-omics analysis combining transcriptomics (miRNA and mRNA profiling) and proteomics (LC-MS).
• Bioinformatic analysis including pathway enrichment and contaminant identification.

Main Results:

• Genetic engineering success confirmed by increased scaffold levels in modified exosomes.
• No significant differences in exosomal miRNA or mRNA content between control and engineered groups.
• Proteomics revealed engineered changes and over 1330 endogenous proteins, with pathway enrichment identified.
• LC-MS effectively detected over 100 cow proteins, highlighting contaminant identification capabilities.

Conclusions:

• A robust dual-omics framework was established for engineered exosome quality control.
• This framework supports the clinical translation of engineered exosomes for therapeutic applications.
• The study underscores the importance of comprehensive analysis for nanomedicine product safety.