Gene Delivery Using Viral Vectors - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 255

Table 5.7 Immune Responses in Viral Gene Transfer

Vector Innate Immune Response Adaptive Immune Response

Adenovirus Inflammation, immunotoxicity in

target organ
Thrombopenia, platelet activation
Hemodynamic changes
Inflammasome-dependent cell death
Induction of inflammatory cytokines
and Interferon-a,b
Activation of Toll-like receptor-9-
dependent and Toll-like receptor-
9-independent pathways of DNA
sensing
Activation of Toll-like receptor-2
NK cell activation
Endothelial cell activation
Complement activation
Dendritic activation (DC)

Pre-existing neutralizing antibody
Neutralizing antibody formation after
vector administration
Transduction of antigen-presenting
cell cytotoxic T-lymphocyte responses
against viral gene products (unless
gutted vectors are used) and transgene
product
Antibody and T-cell responses against
transgene products (especially if non-
specific promoters are used)

AAV Low and highly transient

inflammation
Complement activation
Toll-like receptor-9-dependent DNA
sensing
Dendritic cell activation (DC)

Pre-existing neutralizing antibody
Memory CD8 T-cell responses to
capsid
Neutralizing antibody formation after
vector administration
Antibody and T-cell responses against
transgene product depending on route of
vector administration and other factors
Treg and immune tolerance induction to
the transgene product for hepatic gene
transfer

Lentivirus Interferon-a,b production

Plasmacytoid DC and cDC activa-
tion
Toll-like receptor-7 signaling (?)

Highly efficient transduction of
antigen-presenting cell cytotoxic
T-lymphocyte and antibody responses
against transgene products unless
micoRNA-regulated expression is used
Tolerance induction to transgene prod-
ucts after hepatic gene transfer with
micoRNA-regulated expression cassette

5.8 Biodistribution of Viral Gene Delivery Systems

Noninvasive imaging that provides essential qualitative information regarding the
biodistribution of gene therapy vectors can also be used for the development of tar-
geted vectors. In one report, micro single-photon emission computed tomography has
been used to visualize biodistribution of a 99mTc-polylys-ser-DTPA-biotin-labelled