Antisense as an explanatory, experimental and therapeutic tool for psychiatric disorders

Harrison, Paul J.; Burnet, Philip W. J.

doi:10.1017/s0033291700027276

Cited by 5 publications

(1 citation statement)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A wide variety of antisense oligodeoxynucleotides have been used successfully to block in vivo the expression of functionally important proteins in the nervous system, such as receptors for neurotransmitters and neuropeptides, some of which may be involved in the pathogenesis of certain neurologic or psychiatric disorders (reviewed in [21,23,100,101]). These targets included neurotransmitter receptors, for example the muscarinic [102], D1 dopamine [103], D2 dopamine [104][105][106][107][108], D3 dopamine [25,109,110], D5 dopamine [111], N-methyl-D-aspartate [112,113] and serotonin [114] receptors; peptide receptors, for example the angiotensin type 1 [115][116][117][118], cholecystokinin [119], neuropeptide Y [120], substance P [121] and vasopressin [122] receptors; various subtypes of opioid receptors [123][124][125][126]; steroid receptors, such as the estrogen [127] and progesterone [128,129] receptors, and many other nonreceptor proteins and immediate early genes.…”

Section: Neurology and Psychiatrymentioning

confidence: 99%

Antisense RNA gene therapy for studying and modulating biological processes

Weiss¹,

Davidkova²,

Zhou³

1999

Cellular and Molecular Life Sciences (CMLS)

103

View full text Add to dashboard Cite

Agents that produce their effects through an antisense mechanism offer the possibility of developing highly specific alternatives to traditional pharmacological antagonists, thereby providing a novel class of therapeutic agents, ones which act at the level of gene expression. Among the antisense compounds, antisense RNA produced intracellularly by an expression vector has been used extensively in the past several years. This review considers the advantages of the antisense RNA approach over the use of antisense oligodeoxynucleotides, the different means by which one may deliver and produce antisense RNA inside cells, and the experimental criteria one should use to ascertain whether the antisense RNA is acting through a true antisense mechanism. Its major emphasis is on exploring the potential therapeutic use of antisense RNA in several areas of medicine. For example, in the field of oncology antisense RNA has been used to inhibit several different target proteins, such as growth factors, growth factor receptors, proteins responsible for the invasive potential of tumor cells and proteins directly involved in cell cycle progression. In particular, a detailed discussion is presented on the possibility of selectively inhibiting the growth of tumor cells by using antisense RNA expression vectors directed to the individual calmodulin transcripts. Detailed consideration is also provided on the development and potential therapeutic applications of antisense RNA vectors targeted to the D2 dopamine receptor subtype. Studies are also summarized in which antisense RNA has been used to develop more effective therapies for infections with certain viruses such as the human immunodeficiency virus and the virus of hepatitis B, and data are reviewed suggesting new approaches to reduce elevated blood pressure using antisense RNA directed to proteins and receptors from the renin-angiotensin system. Finally, we outline some of the problems which the studies so far have yielded and some outstanding questions which remain to be answered in order to develop further antisense RNA vectors as therapeutic agents.

show abstract