Documente Academic
Documente Profesional
Documente Cultură
2.1 Protein-Coding
Genes
The concept of gene therapy was originally developed
with the idea of supplying a missing cellular function
by transferring a normal copy of the altered gene into
the relevant cells.
2.1 Protein-Coding
Genes
In reality, in human cells the average size of proteincoding genes is 27 kb, by far longer than the maximum
length fitting the most common gene delivery systems.
For this reason, gene therapy is most commonly based
on the transfer of cDNAs average length:
2.5 kb or of their protein-coding portion (average length:
1.5 kb, corresponding to about 500 codons.
2.1 Protein-Coding
Genes
From the molecular point of view, the transfer of a
gene, or its cDNA or its cDNA coding region has
essentially different properties.
Both cDNAs and their coding portions need to be
transcribed from promoters that are usually different
from the natural ones, which are commonly too large
to be used.
2.1 Protein-Coding
Genes
In addition, the cDNA coding portions alone lack the
regulatory elements controlling gene expression at the
post-transcriptional level, which are usually contained in
the introns or in the untranslated regions (UTRs) at the 3'
and 5' ends of the cDNAs.
These regions are commonly involved in the regulation of
cDNA stability,
transport,
subcellular location and
translation of the cellular mRNAs.
Protein-Coding Genes
in several instances the levels at which proteins are produced
are not very important, and thus a tight translational or
posttranslational regulation of gene expression is not
required.
For example, this is the case of proteins replacing missing
cellular functions in the hereditary disorders of metabolism,
or antigens for anti-cancer vaccination, or secreted
antibodies.
In these cases, transfer of the protein-coding region under the
control of a strong promoter, such as the promoter for the
cytomegalovirus (CMV) immediate-early (TE) genes, is
adequate.
Protein-Coding Genes
In several circumstances, inclusion of a small intron
upstream of the cDNA coding sequence, or of a 3' UTR
downstream of it, are known to facilitate expression of
the protein of interest.
The proteins encoded by the therapeutic genes can
have very different functions, ranging from the
substitution of a missing cellular protein to the
modulation of the immune system.
Cytotoxic T lymphocytes
Lymphocytes that kill other ("target") cells.
Targets may include:
virus-infected cells
cells infected with intracellular bacterial or protozoal
parasites
allografts such as transplanted kidney, heart, lungs, etc
cancer cells
Huntington's
brain
normal
brain
antigen
B lymphocytes,
macrophages,
neutrophils,
http://www.intechopen.com/books/genetherapy-applications
http://nptel.ac.in/courses/102103041/21