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Antisense technology: A review.

ABSTRACT: Antisense technology is beginning to deliver on the broad promise of the technology. Ten RNA-targeted drugs including eight single-strand antisense drugs (ASOs) and two double-strand ASOs (siRNAs) have now been approved for commercial use, and the ASOs in phase 2/3 trials are innovative, delivered by multiple routes of administration and focused on both rare and common diseases. In fact, two ASOs are used in cardiovascular outcome studies and several others in very large trials. Interest in the technology continues to grow, and the field has been subject to a significant number of reviews. In this review, we focus on the molecular events that result in the effects observed and use recent clinical results involving several different ASOs to exemplify specific molecular mechanisms and specific issues. We conclude with the prospective on the technology.

SUBMITTER: Crooke ST

PROVIDER: S-EPMC8005817 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature

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Antisense technology: A review.

Crooke Stanley T ST Liang Xue-Hai XH Baker Brenda F BF Crooke Rosanne M RM

The Journal of biological chemistry 20210101

Antisense technology is beginning to deliver on the broad promise of the technology. Ten RNA-targeted drugs including eight single-strand antisense drugs (ASOs) and two double-strand ASOs (siRNAs) have now been approved for commercial use, and the ASOs in phase 2/3 trials are innovative, delivered by multiple routes of administration and focused on both rare and common diseases. In fact, two ASOs are used in cardiovascular outcome studies and several others in very large trials. Interest in the ...[more]

PMID: 33600796

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Project description:Polyphenol oxidases (PPOs) catalyze the oxidation of phenolics to quinones, the secondary reactions of which lead to oxidative browning and postharvest losses of many fruits and vegetables. PPOs are ubiquitous in angiosperms, are inducible by both biotic and abiotic stresses, and have been implicated in several physiological processes including plant defense against pathogens and insects, the Mehler reaction, photoreduction of molecular oxygen by PSI, regulation of plastidic oxygen levels, aurone biosynthesis and the phenylpropanoid pathway. Here we review experiments in which the roles of PPO in disease and insect resistance as well as in the Mehler reaction were investigated using transgenic tomato (Lycopersicon esculentum) plants with modified PPO expression levels (suppressed PPO and overexpressing PPO). These transgenic plants showed normal growth, development and reproduction under laboratory, growth chamber and greenhouse conditions. Antisense PPO expression dramatically increased susceptibility while PPO overexpression increased resistance of tomato plants to Pseudomonas syringae. Similarly, PPO-overexpressing transgenic plants showed an increase in resistance to various insects, including common cutworm (Spodoptera litura (F.)), cotton bollworm (Helicoverpa armigera (Hübner)) and beet army worm (Spodoptera exigua (Hübner)), whereas larvae feeding on plants with suppressed PPO activity had higher larval growth rates and consumed more foliage. Similar increases in weight gain, foliage consumption, and survival were also observed with Colorado potato beetles (Leptinotarsa decemlineata (Say)) feeding on antisense PPO transgenic tomatoes. The putative defensive mechanisms conferred by PPO and its interaction with other defense proteins are discussed. In addition, transgenic plants with suppressed PPO exhibited more favorable water relations and decreased photoinhibition compared to nontransformed controls and transgenic plants overexpressing PPO, suggesting that PPO may have a role in the development of plant water stress and potential for photoinhibition and photooxidative damage that may be unrelated to any effects on the Mehler reaction. These results substantiate the defensive role of PPO and suggest that manipulation of PPO activity in specific tissues has the potential to provide broad-spectrum resistance simultaneously to both disease and insect pests, however, effects of PPO on postharvest quality as well as water stress physiology should also be considered. In addition to the functional analysis of tomato PPO, the application of antisense/sense technology to decipher the functions of PPO in other plant species as well as for commercial uses are discussed.

Project description:As a precise and efficient genetic engineering method, gene editing technology for animals and plants will gradually move towards large-scale applications, and will have a disruptive impact on the breeding of related traits. By using antisense RNA interference technology to interfere with the mRNA expression and protein translation of the SF-1 gene, we have successfully cultivated tilapia with defective gonadal development. The results of the study showed that the weights of male and female fish in the experimental group were significantly higher than those of the control group. The gonadal weight and gonadal index of the experimental group were significantly lower than those of the control group and the negative control group. HE staining showed that the number of spermatogonia in the testis tissue of the experimental group was significantly reduced, the cavity in the seminiferous tubules was significantly enlarged and increased, the number of sperm cells was significantly decreased, and the number of sperm was relatively rare. However, a large number of stage V oocytes accumulated in the ovarian tissue of female fish in the experimental group, and many of them were gray-white. The mRNA and protein expression levels of SF-1 gene in the gonadal tissues were extremely significantly lower than those of the control and negative controls. The combined analysis of transcriptome and proteome showed that Steroid hormone biosynthesis, Arachidonic acid metabolism and Cell adhesion molecules are involved in the regulation of the gonads of male fish after SF-1 gene silencing. However, ECM-receptor interaction, Retinol metabolism, Nicotinate and nicotinamide metabolism and cytochrome P450 may be involved in the regulation of female fish SF-1 gene silencing. SF-1 silencing may cause developmental defects in the external reproductive organs of male and female fishes and inhibit the development of gonadal tissues through different regulatory pathways. This provides data support for the further functional analysis of SF-1 on fish and the treatment of abnormal human SF-1 expression.

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Antisense technology: A review.

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Antisense technology: A review.

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