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Related Concept Videos

Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

Overview
Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Cells of the Adaptive Immune Response01:23

Cells of the Adaptive Immune Response

The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
Immune Surveillance by NK Cells and Phagocytes01:25

Immune Surveillance by NK Cells and Phagocytes

Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...

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Updated: May 21, 2026

Widespread Transduction of Mouse Neocortical Neurons by Subarachnoid Injection of AAV2
07:40

Widespread Transduction of Mouse Neocortical Neurons by Subarachnoid Injection of AAV2

Published on: May 23, 2025

Insect-Cell-Produced AAV2 Vectors Activate Myeloid Innate Immune Response Featuring NETosis.

Xiaomei Liu1,2, Yifeng Zhou2, Ziwei Tang2

  • 1Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou 215163, Jiangsu, China.

Molecular Pharmaceutics
|May 20, 2026
PubMed
Summary
This summary is machine-generated.

Insect cell-derived recombinant adeno-associated virus (rAAV) triggers neutrophil extracellular trap formation (NETosis), a key immune response. Inhibiting NETosis enhances gene therapy efficacy by reducing inflammation and improving vector transduction.

Keywords:
AAV2 VectorGene TherapyInnate ImmunityNETosisTranscriptomics

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Process Development for the Production and Purification of Adeno-Associated Virus (AAV)2 Vector using Baculovirus-Insect Cell Culture System
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Production, Purification, and Quality Control for Adeno-associated Virus-based Vectors
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Process Development for the Production and Purification of Adeno-Associated Virus (AAV)2 Vector using Baculovirus-Insect Cell Culture System
10:31

Process Development for the Production and Purification of Adeno-Associated Virus (AAV)2 Vector using Baculovirus-Insect Cell Culture System

Published on: January 13, 2022

Production, Purification, and Quality Control for Adeno-associated Virus-based Vectors
09:21

Production, Purification, and Quality Control for Adeno-associated Virus-based Vectors

Published on: January 29, 2019

Area of Science:

  • Gene therapy
  • Immunology
  • Molecular biology

Background:

  • Recombinant adeno-associated virus (rAAV) is a key tool for in vivo gene therapy.
  • Host immune responses to rAAV present challenges for clinical applications.
  • Insect cell systems offer advantages for rAAV production.

Purpose of the Study:

  • To investigate the immunogenicity of insect-cell-derived rAAV2.
  • To identify the immune mechanisms involved in the response to insect-cell-produced rAAV2.
  • To explore strategies for improving rAAV gene therapy safety and efficacy.

Main Methods:

  • Temporal transcriptomic profiling in mice to analyze host immune responses.
  • Functional assays using isolated neutrophils to assess rAAV2-induced NETosis.
  • Evaluation of the impact of DNase I treatment on inflammatory signaling and vector transduction.

Main Results:

  • Insect-cell-derived rAAV2 induced a rapid and sustained innate immune response in mice, characterized by myeloid cell activation.
  • Neutrophil extracellular trap formation (NETosis) pathway was significantly enriched.
  • rAAV2 directly stimulated neutrophils, leading to reactive oxygen species (ROS) production and NET formation.
  • Degradation of extracellular DNA with DNase I reduced hepatic inflammation and improved rAAV2 transduction.

Conclusions:

  • NETosis is a previously unrecognized immune mechanism triggered by insect-cell-produced AAV vectors.
  • NET formation acts as a biological barrier to rAAV-mediated gene transfer.
  • Targeting NETosis presents a potential strategy to enhance the safety and efficacy of AAV-based gene therapies.