AAVR disruption as a producer-cell engineering strategy for enhanced supernatant-based recovery of selected AAV serotypes.

Kenji Sakamoto, Kouhei Yoshida, Yuji Tsunekawa, Naymel A Guzman Mendoza, Yui Komaki, Azusa Onodera, Takashi Okada

Abstract read

In one paragraph

Article in Molecular therapy. Advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

7 authors.

Kenji SakamotoDivision of Molecular and Medical Genetics, Center for Gene and Cell Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Kouhei YoshidaDivision of Molecular and Medical Genetics, Center for Gene and Cell Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Yuji TsunekawaDivision of Molecular and Medical Genetics, Center for Gene and Cell Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Naymel A Guzman MendozaDivision of Molecular and Medical Genetics, Center for Gene and Cell Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Yui KomakiDivision of Molecular and Medical Genetics, Center for Gene and Cell Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Azusa OnoderaDivision of Molecular and Medical Genetics, Center for Gene and Cell Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Takashi OkadaDivision of Molecular and Medical Genetics, Center for Gene and Cell Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recovery of adeno-associated virus (AAV) vectors from culture supernatants has attracted increasing interest as a strategy to simplify downstream processing and improve product purity. However, several AAV serotypes can be re-internalized by producer cells, raising the possibility that newly released particles are recaptured during production and thereby limiting extracellular yield. Because AAV entry is mediated by the universal receptor KIAA0319L (AAVR), receptor-dependent re-uptake may contribute to this limitation, yet its role in vector manufacturing remains unexplored. Here, we investigated whether disruption of AAVR enhances supernatant-based AAV recovery. Using CRISPR-Cas9-mediated genome editing, we generated AAVR-knockout (AAVR-KO) HEK293-EB producer cells by deleting exon 2 containing the translational start codon. AAVR ablation abolished susceptibility to multiple AAV serotypes and markedly reduced cellular uptake of extracellular particles. In supernatant AAV vector recovery assays, AAVR knockout increased supernatant vector genome recovery for selected serotypes in a representative clone, although this effect varied among independently isolated clones. Complementary AAVR overexpression reduced accumulation of extracellular AAV1 vector genomes, supporting a role for AAVR expression levels in supernatant recovery while also suggesting additional effects on production-related cellular processes. These findings identify AAVR-dependent cellular uptake or retention as a modifiable post-release process that can influence supernatant-based AAV vector recovery.

Indexed as

AAVRAAV vector productionadeno-associated virusHEK293 producer cellsKIAA0319Lproducer-cell engineeringreceptor-mediated uptakesupernatant recoveryvector genome titer

Identifiers

PMID42662409

DOI10.1016/j.omta.2026.201830

PMCPMC13519645

What Socratic holds

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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 Socratic graph.