ArticleBiotechnology and bioengineering2023
Design space determination to optimize DNA complexation and full capsid formation in transient rAAV manufacturing.
Article in Biotechnology and bioengineering, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Development of an inducible stable producer cell line for rAAV production.Biochemical engineering journal · 2026Article
- Manufacture of adeno-associated virus vectors by a novel human-derived cell line HAT and comprehensive evaluation of the vectors.Molecular therapy. Advances · 2026Article
- Mixture design as a tool for improving full-to-empty particle ratios across various GOIs in rAAV production.Gene therapy · 2026Article
- Quantifying the Full-to-Empty Adeno-Associated Virus (AAV) Capsid Ratios and Their Impact on Transduction Efficiency in vitro.The AAPS journal · 2025Article
- Characterization of difficult-to-remove host cell proteins in adeno-associated virus downstream processing.Molecular therapy. Methods & clinical development · 2025Article
- Improved productivity of recombinant adeno-associated virus (rAAV) via triple transfection of HEK293 cells using perfusion cultivation.Bioprocess and biosystems engineering · 2025Article
- Development of an HEK293 Suspension Cell Culture Medium, Transient Transfection Optimization Workflow, and Analytics for Batch rAAV Manufacturing.Biotechnology and bioengineering · 2025Article
- Chromatography in Downstream Processing of Recombinant Adeno-Associated Viruses: A Review of Current and Future Practises.Biotechnology and bioengineering · 2025Review
- Development of inducible packaging cell line for rAAV production via CRISPR-Cas9 mediated site-specific integration.Biochemical engineering journal · 2025Article
- Unlocking DOE potential by selecting the most appropriate design for rAAV optimization.Molecular therapy. Methods & clinical development · 2024Article
- Biolayer interferometry for adeno-associated virus capsid titer measurement and applications to upstream and downstream process development.Molecular therapy. Methods & clinical development · 2024Article
- Quantification of full and empty particles of adeno-associated virus vectors via a novel dual fluorescence-linked immunosorbent assay.Molecular therapy. Methods & clinical development · 2024Article
- Enhanced ER protein processing gene expression increases rAAV yield and full capsid ratio in HEK293 cells.Applied microbiology and biotechnology · 2024Article
- Producing high-quantity and high-quality recombinant adeno-associated virus by low-cis triple transfection.Molecular therapy. Methods & clinical development · 2024Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Recombinant adeno-associated virus (rAAV) vectors are a promising platform for in vivo gene therapies. However, cost-effective, well-characterized processes necessary to manufacture rAAV therapeutics are challenging to develop without an understanding of how process parameters (PPs) affect rAAV product quality attributes (PQAs). In this work, a central composite orthogonal experimental design was employed to examine the influence of four PPs for transient transfection complex formation (polyethylenimine:DNA [PEI:DNA] ratio, total DNA/cell, cocktail volume, and incubation time) on three rAAV PQAs related to capsid content (vector genome titer, vector genome:capsid particle ratio, and two-dimensional vector genome titer ratio). A regression model was established for each PQA using partial least squares, and a design space (DS) was defined in which Monte Carlo simulations predicted < 1% probability of failure (POF) to meet predetermined PQA specifications. Of the three PQAs, viral genome titer was most strongly correlated with changes in complexation PPs. The DS and acceptable PP ranges were largest when incubation time and cocktail volume were kept at mid-high setpoints, and PEI:DNA ratio and total DNA/cell were at low-mid setpoints. Verification experiments confirmed model predictive capability, and this work establishes a framework for studying other rAAV PPs and their relationship to PQAs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.