Gene Delivery Using Physical Methods - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 85

Table 3.1 Comparison Among Biological, Chemical, and Physical Methods of Gene Delivery

S. No. Gene Delivery

Method

Advantages Disadvantages

1 Biological method

(viral and bacterial
vectors)

l High transfection efficiency in
dividing and nondividing cells
l Possible targeted delivery

l Not easy to manufacture

Not easy to manufacture
and require cold storage
l Cumbersome quality

Possible targeted delivery
l Systemic delivery﻽possible

Cumbersome quality
control requirement
l High cost,

Systemic delivery﻽possible
l Stable expression

Stable expression High cost,

immunogenecity and
oncogenecity risks
l Size of gene to be

Size of gene to be
inserted﻽limited

2 Chemical methods

(nonviral chemical
vectors)

l High

High in vitro transfection
achieved
l Possible

l �ow

�ow in vivo transfection
efficiency
l �ow efficiency in

Possible in vivo organ targeting
l Simple to manufacture in small

�ow efficiency in
primary and nondividing
cells
l �imited clinical success

Simple to manufacture in small
batches and storage conditions
are more flexible
l �ess costly

�imited clinical success
l Consistent reproducible

�ess costly
l �ess limit on gene size

Consistent reproducible
large scale
manufacturing﻽not easy
to achieve

�ess limit on gene size
l Higher reproducibility compared

Higher reproducibility compared
to biological vectors
l High commercial interest

High commercial interest

3 Physical

methods

l Higher local tissue transfection

Higher local tissue transfection
efficiency
l Transfection in all cell types,

l Need for a specific

Need for a specific
instrument
l Need of parameter

Transfection in all cell types,
even in difficult to transfect cells,
is achievable
l Easy process standardization

Need of parameter
optimization for different
types of cells
l Higher tissue damage

Easy process standardization
l �ess limit on gene size

Higher tissue damage
observed �ess limit on gene size

l Mostly

Mostly ex vivo applicable

Although the transgene expression level was relatively low, it was sufficient to
achieve vaccination, and this report formed a further basis for generating antivi-
ral immune responses by intramuscular injection of plasmids encoding viral anti-
gens. These immune responses in animals against various infectious agents led to
the development of therapeutic DNA vaccines [10] . Today, the world of DNA vac-
cines has reached the level of clinical trials against various diseases, including AIDS,
tumor, and other viral infectious agents, by direct injection of plasmid DNA into
skeletal muscles.
The level of gene expression is significantly governed by the method of plasmid
injection. An injection guided by intense illumination along the longitudinal axis
of the mouse quadriceps muscle and parallel to the myofibers has shown 200-fold
higher levels of luciferase expression than perpendicular injection [11] . Recently, the
plasmid DNA injection was also used for expressing biological macromolecules as