Biomedical Engineering Reference
In-Depth Information
d
n
4
y
3
n
g
|
3
Scheme 4.9
Synthesis of
L
-lysine-based peptide dendrimers.
4.5 Polypeptide Gene Vectors
Among various nonviral gene delivery methods, using natural or artificial
polypeptides with certain biological functions is considered as one promising
approach. Unlike other vectors, polypeptides have low cytotoxicity, greater
biodegradability, and also serve different functions. For example, lysine- and/
or arginine-rich cationic peptides can condense DNA into compact particles,
TAT-based cell-penetrating peptides can disrupt the endosomal membrane,
nuclear localization signal (NLS) peptides can traffic DNA to the nucleus, and
RGD-rich peptides can target polyplexes to specific receptors. These properties
may all be part of a single peptide sequence or a combination of peptides
chemically conjugated to form a vector capable of packaging and targeting
DNA for efficient delivery.
4.5.1 Normal Peptide-Based Vectors
Polypeptide-based vectors have great potential for gene delivery, as numerous
new functional peptides will be continually discovered, and they have the
ability to achieve these goals alone or in combination with other systems. The
approach of introducing ligands that lead gene vectors to target caveolae-
mediated endocytosis on a nanoparticle surface might serve as a promising
strategy for effective gene transfection. Recently, in an attempt to enhance the
possibility of caveolae-mediated endocytosis, Liu et al. demonstrated a
peptide-targeted gene vector for highly efficient receptor-mediated intracellular
