Cells · 1 author, 2 centres
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This narrative review describes how host cell restriction factors, including innate immune sensors and intrinsic antiviral proteins, can detect and block the transduction of lentiviral (LV) and adeno-associated virus (AAV) gene therapy vectors, thereby reducing their efficacy.
This narrative review discusses how host cell restriction factors (RFs) can hinder the efficacy of lentiviral (LV) and adeno-associated virus (AAV) vectors used in gene therapy. The background explains that gene therapy vectors, while promising, must evade a complex array of host cellular defenses evolved to protect against pathogens. The review details mechanisms by which pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and cytosolic DNA sensors (e.g., cGAS), detect vector nucleic acids, triggering innate immune responses that upregulate interferons and pro-inflammatory cytokines. It also covers intrinsic RFs like TRIM5α, APOBEC3, and SAMHD1 that directly interfere with the viral life cycle. Key results summarize the specific vectors, viral components (e.g., RNA, reverse transcription intermediates, capsid proteins), and cellular sensors involved for both LV and AAV vectors. For AAV, additional barriers include capsid degradation via phosphorylation and SUMOylation, and genome conversion blockades by factors like FKBP52.
