Biomedical Engineering Reference
In-Depth Information
5
Gene Delivery Using Viral Vectors
Deepa H. Patel, Ambikanandan Misra
Pharmacy Department, TIFAC - Centre of Relevance and Excellence in New
Drug Delivery Systems, The Maharaja Sayajirao University of Baroda,
PO Box 51, Kalabhavan, Vadodara 390 001, Gujarat, India
5.1 Introduction
Transfection of naked DNA to living cells has been used as a classical method for
molecular genetics experiments and gene therapy for many years. However, with a better
understanding of immune response and the viral life cycle, transferring genetic mate-
rial using viral vectors (called transduction) has evolved as an advanced technology for
efficient gene delivery. In addition to an arduous production process and immunogenic
response, viral vectors have the potential to circumvent the drawbacks of chemical trans-
fection like inefficient and limited delivery only to actively proliferating cells. Viruses
have complex structures and life cycles and many are pathogens, but several viruses are
highly efficient gene delivery vehicles. Nonviral vectors generally cannot approach the
efficiency of viral vectors when considered on the basis of gene copies that must be pre-
sented to the target cell in order that one or several copies can be expressed in the cell
nucleus. For viral vectors, the usual approach is to remove the unneeded or pathogenic
features of the virus while retaining the efficiency of gene delivery, expression, and per-
sistence wherever appropriate. Designing viral vectors addresses many common consi-
derations for both safety and biological activity, including removal of virulent genes,
absence of the replication component of the parental virus, and host responses to compo-
nents of the vector. Also, specific applications of individual classes of vectors require the
properties of the parental virus, the target organ or disease, and the gene to be delivered.
Pathogenic viruses are occasionally used as vectors after neutralizing their pathogenicity.
The process involves the deletion of a part of the viral genome critical for viral replication.
Such a virus can efficiently target cells without causing pathogenicity and disturbances
in cell physiology. These vectors have targeting ability for a wide range of cells, but for
certain applications, viral vectors are engineered to target specific cells only. However,
some viruses can rapidly rearrange their genomes, resulting in genetic instability, which
makes predicting the virus's cell-specific targeting ability and its reproducibility for gene
delivery disadvantageous. Hence, work using such a viral vector should be avoided.
For example, retrovirus vectors integrate into cells efficiently, so insertional mutagene-
sis was considered as an important issue. Adenovirus vectors (Ad) generate significant
host cellular immune responses and require strategies to remove or prevent expression
of adenovirus genes, or possibly to develop approaches to transient immune modulation.
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