Biomedical Engineering Reference
In-Depth Information
2.6
Cell surface receptor
interaction and cellular
uptake of DNA delivery
system by target cells
through endocytosis
By interacting with the DNA delivery system,
cell surface proteoglycans and mucus reduce
transfection. The cellular uptake by endocytosis
influences the transgene expression and
therapeutic effect of the DNA
Ligand-based receptor-mediated
endocytosis and cationically charged
DNA delivery system enhances cellular
association and endocytosis of the
DNA delivery system.
[43]
3.
Intracellular barriers to the DNA delivery system
[43,44]
3.1
Endosomal escape and
lysosomal degradation of
DNA
Avoidance of DNA degradation and release
from the carrier system before trafficking to
the lysosome occurs. If DNA is not released
from the endosome, it becomes degraded in the
lysosome.
Use of fusion lipids such as DOPE,
cholesterol, endosomolytic agents
such as chloroquine, and viral peptides
enhances DNA release from the
endosome
3.2
Cytoplasmic stability and
trafficking of DNA
Against intracellular DNAse and trafficking
toward nuclear envelope.
DNA associated with the carrier,
such as protamine sulfate, PEI, etc.,
enhances stability against cytosolic
DNAse and enhances nuclear
trafficking
[43,44]
3.3
Nuclear transport of DNA
Small gaps in nuclear envelope hinder
nuclear transport of DNA, with reduced DNA
expression
Use of a nuclear localization
signal such as protamine sulphate,
polyarginines, polyhistidines, etc.,
enhances nuclear transport of DNA
[42-45]
3.4
Transgene expression and
posttranslational changes
in protein
Promoter and DNA sequence determine the
expression
[45]
4
Biological immune
barriers
Certain DNA sequences cause immune
response to DNA and vectors
Altering the DNA sequence to remove
immune factor.
[37-
41,43]
5
Scale up barriers
Barriers during scale up and launching the gene
delivery product and clinical trials and approval
from FDA.
Proper management of preclinical and
clinical studies with documentation
[46]
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