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MicroRNA-regulated viral vectors for gene therapy
#MMPMID27226955
Geisler A
; Fechner H
World J Exp Med
2016[May]; 6
(2
): 37-54
PMID27226955
show ga
Safe and effective gene therapy approaches require targeted tissue-specific
transfer of a therapeutic transgene. Besides traditional approaches, such as
transcriptional and transductional targeting, microRNA-dependent
post-transcriptional suppression of transgene expression has been emerging as
powerful new technology to increase the specificity of vector-mediated transgene
expression. MicroRNAs are small non-coding RNAs and often expressed in a tissue-,
lineage-, activation- or differentiation-specific pattern. They typically
regulate gene expression by binding to imperfectly complementary sequences in the
3' untranslated region (UTR) of the mRNA. To control exogenous transgene
expression, tandem repeats of artificial microRNA target sites are usually
incorporated into the 3' UTR of the transgene expression cassette, leading to
subsequent degradation of transgene mRNA in cells expressing the corresponding
microRNA. This targeting strategy, first shown for lentiviral vectors in antigen
presenting cells, has now been used for tissue-specific expression of
vector-encoded therapeutic transgenes, to reduce immune response against the
transgene, to control virus tropism for oncolytic virotherapy, to increase safety
of live attenuated virus vaccines and to identify and select cell subsets for
pluripotent stem cell therapies, respectively. This review provides an
introduction into the technical mechanism underlying microRNA-regulation,
highlights new developments in this field and gives an overview of applications
of microRNA-regulated viral vectors for cardiac, suicide gene cancer and
hematopoietic stem cell therapy, as well as for treatment of neurological and eye
diseases.
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