Biomedical Engineering Reference
In-Depth Information
Although viruses are currently the most commonly researched
vector,
because
of
continuing
safety
concerns
research
has
6
broadened for developing non-viral alternatives.
Non-viral vectors
have advantages that they do not integrate into chromosome, can
introduce DNA into non-dividing cells, have low immunogenicity,
have ability to deliver large genes, have no infective risk, and are
significantly less expensive, easy to handle, and, most importantly,
have possibility for large-scale production at reasonable cost.
7
Non-viral systems offer several advantages, but they are also
associated with few major disadvantages, including toxicity and low
transfection efficiency, since the non-viral delivery vectors have to
overcome intracellular barriers, such as endosomes and nuclear
membranes.
8
Thus, the most challenging task is to design non-viral
gene delivery vectors with low cytotoxicity and high transfection
efficiency. Non-viral molecular carriers include polycation (mainly
ion-based/cationic polymers and lipids delivery system) to assist
the passage of DNA to the cell's nucleus.
In the late 1950s, the earliest cationic polymer vector for
gene delivery was originated to enhance nucleic acid to enter the
cells. Thereafter, in 1965, dextran was used in gene delivery as the
simple, effective, and widely used polymer.
6
9
Cationic polymers were
intensively studied as non-viral gene vectors since the first successful
clinical gene therapy of adenosine deaminase deficiency in 1989.
10
Cationic vectors with diminished cytotoxicity and enhanced efficacy
are rapidly emerging as systems of choice. Presently, polycations
used as gene delivery systems are mostly polyamines that contain
primary, secondary, or tertiary amines. Major cationic polymers that
are commonly used in gene delivery include poly(L-lysine) (PLL),
polyethyleneimine (PEI), dendrimers, cationic polysaccharides,
etc.
11-13
2.2
Cationic Polymer Targeted Delivery
of Nucleotides
Delivery of therapeutic nucleotides to the target is possible through
various methods and mechanisms. Cationic polymers are leading
class of non-viral gene delivery systems due to their versatility in
MW, polymer type, molecular architecture, and ability to introduce
target-specific moieties. The degradation of these polymers releases
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