RESUMO
Antisense oligonucleotides (ASO), short single-stranded polymers based on DNA or RNA chemistries and synthesized in vitro, regulate gene expression by binding in a sequence-specific manner to an RNA target. The functional activity and selectivity in the action of ASOs largely depends on the combination of nitrogenous bases in a target sequence. This simple and natural property of nucleic acids provides an attractive route by which scientists can create different ASO-based techniques. Over the last 50 years, planned and realized applications in the field of antisense and nucleic acid nanotechnologies have produced astonishing results and posed new challenges for further developments, exemplifying the essence of the post-genomic era. Today the majority of ASOs are chemically modified and/or incorporated within nanoparticles to enhance their stability and cellular uptake. This review critically analyzes some successful cases using the antisense approach in medicine to address severe diseases, such as Duchenne muscular dystrophy and spinal muscular atrophy, and suggests some prospective directions for future research. We also examine in detail the elaboration of unmodified insect-specific DNA insecticides and RNA preparations in the areas of agriculture and forestry, a relatively new branch of ASO that allows circumvention of the use of non-selective chemical insecticides. When considering the variety of successful ASO modifications with an efficient signal-to-noise ratio of action, coupled with the affordability of in vitro oligonucleotide synthesis and post-synthesis procedures, we predict that the next half-century will produce a fruitful yield of tools created from effective ASO-based end products.
Assuntos
Agentes de Controle Biológico/farmacologia , Mariposas/efeitos dos fármacos , Atrofia Muscular Espinal/terapia , Distrofia Muscular de Duchenne/terapia , Fármacos Neuromusculares/uso terapêutico , Oligonucleotídeos Antissenso/genética , Agricultura/métodos , Animais , Agentes de Controle Biológico/síntese química , Agentes de Controle Biológico/história , DNA/antagonistas & inibidores , DNA/genética , DNA/metabolismo , Agricultura Florestal/métodos , Regulação da Expressão Gênica/efeitos dos fármacos , História do Século XX , História do Século XXI , Humanos , Larva/efeitos dos fármacos , Larva/genética , Larva/metabolismo , Mariposas/genética , Mariposas/crescimento & desenvolvimento , Mariposas/metabolismo , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/metabolismo , Atrofia Muscular Espinal/patologia , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/patologia , Nanopartículas/administração & dosagem , Nanopartículas/química , Fármacos Neuromusculares/síntese química , Fármacos Neuromusculares/história , Oligonucleotídeos Antissenso/síntese química , Oligonucleotídeos Antissenso/metabolismo , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Baculovirus IAP (inhibitor-of-apoptosis) genes originated by capture of host genes. Unmodified short antisense DNA oligonucleotides (oligoDNAs) from baculovirus IAP genes can down-regulate specific gene expression profiles in both baculovirus-free and baculovirus-infected insects. In this study, gypsy moth (Lymantria dispar) larvae infected with multiple nucleopolyhedrovirus (LdMNPV), and LdMNPV-free larvae, were treated with oligoDNA antisense to the RING (really interesting new gene) domain of the LdMNPV IAP-3 gene. The results with respect to insect mortality, biomass accumulation, histological studies, RT-PCR, and analysis of DNA apoptotic fragmentation suggest that oligoRING induced increased apoptotic processes in both LdMNPV-free and LdMNPV-infected insect cells, but were more pronounced in the latter. These data open up possibilities for promising new routes of insect pest control using antisense phosphodiester DNA oligonucleotides.
Assuntos
Controle de Insetos/métodos , Mariposas/virologia , Nucleopoliedrovírus/genética , Oligodesoxirribonucleotídeos Antissenso , Animais , Apoptose , Genes Virais/genética , Larva/virologia , Transcriptoma , Proteínas Virais/genéticaRESUMO
Having observed how botanicals and other natural compounds are used by nature to control pests in the environment, we began investigating natural polymers, DNA and RNA, as promising tools for insect pest management. Over the last decade, unmodified short antisense DNA oligonucleotides have shown a clear potential for use as insecticides. Our research has concentrated mainly on Lymantria dispar larvae using an antisense oligoRING sequence from its inhibitor-of-apoptosis gene. In this article, we propose a novel biotechnology to protect plants from insect pests using DNA insecticide with improved insecticidal activity based on a new antisense oligoRIBO-11 sequence from the 5.8S ribosomal RNA gene. This investigational oligoRIBO-11 insecticide causes higher mortality among both L. dispar larvae grown in the lab and those collected from the forest; in addition, it is more affordable and faster acting, which makes it a prospective candidate for use in the development of a ready-to-use preparation.