Litt om virus og PCI-teknologien.
https://www.researchgate.net/publication/339426900_Photochemical_Internalization_for_Intracellular_Drug_Delivery_From_Basic_Mechanisms_to_Clinical_Research
"6.2. Viral Gene Delivery Systems
Viral systems are commonly used for the delivery of therapeutic genes to cells, both for
transient expression, and with the aim of stable integration of a transgene into the genome of a target
cell. As compared to non-viral delivery vehicles viral systems are usually more efficient, among
other things due to enhanced uptake into cells, and inherent functions for endosomal escape and
nuclear trafficking. However, many viral systems have severe safety concerns, and in general it
would be very advantageous to be able to target virus-mediated gene delivery to the desired sites in
the body, and also to use as low doses of virus as possible to diminish production problems, safety
concerns and the induction of unwanted immune reactions. For many virus types endocytosis is an
important mechanism for uptake into the cell, and although most viruses as part of their life cycle
have endogenous mechanisms for endosomal escape of their genetic material, these mechanisms
may not always be fully efficient. Thus, the use of PCI for enhancing virus-mediated gene delivery
has been explored with two commonly used viral gene delivery systems where endocytosis is
known to play an important role for cellular uptake. Adenovirus serotype 5 (Ad5) is usually taken
up into the cell by endocytosis after binding the coxsackievirus and adenovirus receptor (CAR)
receptor, and it was generally believed that after uptake most viral particles escape from the
endosomes [202,203]. It was therefore somewhat surprising that PCI could strongly enhance
adenovirus-mediated transduction, with an enhancement of >20 times achieved by the employment
of PCI [204,205]. In the same study dose response experiments showed that the
transduction-enhancing effect of PCI was especially good at low virus doses, something that may be
very valuable in the clinical use of adenovirus mediated therapies. Uptake by the CAR receptor in
many cases represents a limitation for Ad5-mediated gene delivery, since many potentially
important target cells (e.g., airway epithelial cells, smooth muscle cells and most cancer cells) have
low expression of this receptor. However, uptake of Ad5 in CAR-negative cells can be enhanced
un-specifically by coating the virus particles by cationic polymers [206,207], or, specifically, by
furnishing the virus surface with a ligand for a specific receptor on the target cell surface. PCI should
be well suited both for enhancing the efficacy and the site-specificity of Ad5 mediated gene
transduction with such methods, and in several studies a strong PCI-induced enhancement has been
achieved for both polycation-mediated [208,209] and for receptor-mediated [210] uptake of Ad5
virus particles.
Adenovirus associated virus (AAV) is a commonly used vector for permanent transduction of
cells: AAV is usually taken into the cell by endocytosis and for several types of AAV endosomal
trafficking has been described to be a limiting factor in the transduction process [211,212]. Thus, a
study was performed using PCI for enhancing AAV-mediated gene delivery to glioblastoma cells,
and it was shown that PCI could enhance transduction also for this virus type [213]. "