Targeting
Strategies in Cancer Gene Therapy
WANG Jin-Hui, LIU Xin-Yuan*
( Institute of Biochemistry and Cell Biology, Shanghai
Institutes for Biological Sciences,
the Chinese Academy of Sciences, Shanghai 200031, China )
Abstract Targeting to the tumor tissues can
improve the therapeutic effect of gene transfer by preventing damage of healthy
tissues and decreasing the risk of germ line transduction. Although targeting
seems not important for intratumoral gene delivery, it becomes crucial when
systemic gene transfer is performed. Targeted gene therapy of malignancies can
be achieved through targeted gene delivery or targeted gene transcription.
Recent advances in targeted delivery include the successful use of bifunctional
crosslinkers to target adenoviral and retroviral vectors, inserting short
targeting peptides and larger polypeptide-binding domains into the coat
proteins of a number of different viral vectors, and replication-competent
vectors which have been shown to be promise as anti-cancer agents. Some other
non-viral therapeutic agents, including receptor-mediated DNA or liposome-DNA
complex, and bacteria vehicles have also been developed. Some of these delivery
systems are currently in clinical trials. For targeted and regulable gene
transcription, tissue or tumor specific promoters and some manual regulatory
systems are used to regulate therapeutic gene expression. Antisense
oligonucleotides, some ribozyme and DNAzyme molecules are developed to
inactivate genes that are essential to the development of many tumors.
Key
words targeting; gene therapy;
cancer
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