Biomedical Engineering Reference
In-Depth Information
7.8.1.2 Lentivirus
Lentiviruses are a subclass of retroviruses and hence are also RNA viruses. These
have recently been developed as viral vectors and have the potential to infect both
dividing and nondividing cells. This feature is unique to lentiviruses that use inte-
grase enzyme to transduce host cells. These vectors also require integration into the
host genome for the expression of the vector. Oligonucleotides of size up to 8 kB
can be packed into a lentiviral vector. They possess high transduction efficiency and
mutagenic potential [154,155] . HIV-based lentiviral vectors have been successfully
tried against AIDS [155] .
7.8.1.3 Adenovirus
Adenovirus is a DNA virus commonly used as an AS ODN vector. Replication defi-
cient adenoviruses with a deleted E1A region are used as viral vectors. The E1A region
is essential for the replication of these viruses. Such vectors can infect a cell only once
and can infect both dividing and nondividing cells. They possess high transduction effi-
ciency and can carry oligonucleotides of size up to 8 kB [154,155] . As with retrovirus
and lentivirus, adenoviruses do not integrate into the host genome and hence are not
replicated during cell division. Thus, these vectors possess low mutagenic potential but
may pose severe immunological risks due to the expression of viral proteins in the host
cells following vector administration.
7.8.1.4 Adeno-Associated Viruses
Adeno-associated virus is a small virus that infects humans and other species and
requires coinfection with either adenovirus or herpesvirus for replication. These
can infect both dividing and resting cells, with site-specific integration into the host
genome, and so they possess low mutagenic potential. These vectors cannot incorpo-
rate oligonucleotides larger than 5 kB but are capable of infecting multiple types of
cells [154,156] .
7.8.2  Nonviral Delivery Techniques
Transfection is the term used to describe intracellular delivery of antisense agents
using nonviral vectors. The oncogenic consequences and immunological risks asso-
ciated with the viral vectors have led to the development of novel nonviral vectors for
antisense drug delivery. Although nonviral vectors are safer than viral vectors, they
impart low and transient transfection efficiency. Along with the chemical modifica-
tions, the conjugation and/or incorporation of targeting ligands like peptides, mono-
clonal antibodies, and so on, are essential to achieve the desired therapeutic effect.
Cationic lipids/polymers and cell-penetrating peptides are commonly used to design
these delivery vectors ( Table 7.6 ).
The positive charge of these delivery systems facilitates complexation with
negatively charged oligonucleotides or siRNA and ionic interaction with cell
membranes.
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