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Updated: Jul 1, 2025
Direct Intrathecal Injection of Recombinant Adeno-associated Viruses in Adult Mice
Published on: February 15, 2019
Use of adeno-associated viruses for transgenic modulation of microglia structure and function: A review of technical
Jayson B Ball1, Matthew G Frank1, Suzanne M Green-Fulgham1
1Department of Psychology and Neuroscience, and the Center for Neuroscience, University of Colorado, Boulder, CO 80309, USA.
Abstract:
Microglia play a central role in the etiology of many neuropathologies. Transgenic tools are a powerful experiment approach to gain reliable and specific control over microglia function. Adeno-associated virus (AAVs) vectors are already an indispensable tool in neuroscience research. Despite ubiquitous use of AAVs and substantial interest in the role of microglia in the study of central nervous system (CNS) function and disease, transduction of microglia using AAVs is seldom reported. This review explores the challenges and advancements made in using AAVs for expressing transgenes in microglia. First, we will examine the functional anatomy of the AAV capsid, which will serve as a basis for subsequent discussions of studies exploring the relationship between capsid mutations and microglia transduction efficacy. After outlining the functional anatomy of AAVs, we will consider the experimental evidence demonstrating AAV-mediated transduction of microglia and microglia-like cell lines followed by an examination of the most promising experimental approaches identified in the literature. Finally, technical limitations will be considered in future applications of AAV experimental approaches.
Insights
Adeno-associated virus (AAV) vectors are crucial for neuroscience, but efficiently targeting microglia remains challenging. This review details AAV capsid anatomy, transduction methods, and limitations for microglia research in neuropathology.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Microglia are central to neuropathology.
- Adeno-associated virus (AAV) vectors are essential neuroscience tools.
- Targeting microglia with AAVs for gene expression is difficult.
Purpose of the Study:
- To review challenges and advancements in using AAVs for microglia transduction.
- To explore AAV capsid anatomy and its impact on microglia targeting.
- To examine experimental evidence and approaches for AAV-mediated microglia gene expression.
Main Methods:
- Review of existing literature on AAV vectors and microglia.
- Analysis of AAV capsid structure-function relationships.
- Examination of experimental studies on microglia and microglia-like cell line transduction.
- Identification of promising experimental approaches.
Main Results:
- AAV capsid anatomy influences microglia transduction efficiency.
- Specific capsid mutations can enhance microglia targeting.
- Various experimental strategies show promise for AAV-mediated microglia gene expression.
- Technical limitations still exist for widespread AAV application in microglia.
Conclusions:
- Understanding AAV capsid biology is key to improving microglia transduction.
- Further research is needed to overcome limitations in AAV-based microglia gene therapy.
- Advancements in AAV technology hold potential for studying CNS diseases.
