RESUMO
We investigated the effects of hepatitis B virus (HBV) S/C double gene loci antisense locked nucleic acid on replication and expression of HBV in hepatitis transgenic mice. HBV mice (N = 30) were randomly divided into five groups of six mice: 5% glucose solution control, empty liposome control, single-target S, single-target C, and dual-target SC groups. An antisense locked nucleic acid fragment was injected into the mice. Serum HBsAg, serum HBV DNA, HBV C-mRNA expression in liver tissue, HbsAg and HbcAg expression in hepatocytes, serum albumin, alanine transaminase (ALT), urea nitrogen, and creatinine were detected. Liver and kidney sections were examined for the effects of antisense locked nucleic acid. The expression of HBsAg was markedly inhibited; the inhibition rates of the S, C, and SC target groups were 36.63, 31.50, and 54.87%, respectively; the replication of HBV DNA was also inhibited: 23.97, 21.13, and 35.83%, respectively. After injection at 1, 3, and 5 days, the corresponding rates for HBsAg inhibition were 14.40, 25.61, and 31.33%, and for HBV DNA inhibition they were 11.04, 19.24, and 24.13%. Compared with the control group, the differences in serum albumin, ALT, urea nitrogen, and creatinine in each group were not statistically significant, and the number of HbsAg- and HBcAg-positive cells in the mouse liver was significantly reduced. The liver and kidney tissues were normal. The gene therapy had significant inhibitory effects on the replication and expression of HBV in transgenic mice, and double-gene targeting was better than single-gene targeting.
Assuntos
DNA Antissenso/genética , Antígenos do Núcleo do Vírus da Hepatite B/genética , Antígenos de Superfície da Hepatite B/genética , Hepatite B/virologia , Animais , DNA Antissenso/administração & dosagem , DNA Antissenso/toxicidade , Modelos Animais de Doenças , Regulação Viral da Expressão Gênica , Hepatite B/sangue , Hepatite B/patologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Humanos , Testes de Função Renal , Testes de Função Hepática , Camundongos , Camundongos Transgênicos , RNA Mensageiro/genética , Carga Viral , Replicação Viral/genéticaRESUMO
Thioredoxin h is closely related to germination of cereal seeds. The mechanism of transgenic wheat seeds with antisense trxs gene, which is responsible for low germination rate was studied through analyzing the changes in proteins of wheat seeds during germination. The antisense trxs could weaken the metabolism of wheat seeds by decreasing the quantity of proteins involved in metabolism, while chloroform-methanol (CM) protein fraction consisted mostly of some low molecular weight proteins (<20 kD). Compared with wild-type wheat seeds, the folding of glutenin in transgenic wheat ones was affected during the wheat maturating. Big glutenin macropolymers could be formed more easily in transgenic wheat seeds than in wild-type wheat ones. Therefore, the degradation speed of glutenin in transgenic wheat seeds was slower than that in wild-type wheat ones during seed germination. In addition, the degradation of some proteins in transgenic wheat embryos was also delayed during germination.
Assuntos
DNA Antissenso/toxicidade , Germinação/fisiologia , Plantas Geneticamente Modificadas/metabolismo , Tiorredoxinas/antagonistas & inibidores , Triticum/metabolismo , DNA Antissenso/genética , DNA Antissenso/metabolismo , Endoderma/metabolismo , Cloreto de Potássio/química , Sementes/metabolismo , Sementes/fisiologia , Solubilidade , Tiorredoxinas/genética , Tiorredoxinas/metabolismo , Tiorredoxinas/toxicidade , Triticum/genéticaRESUMO
BACKGROUND: Transgenic mice bearing a murine immunoglobulin enhancer/c-myc fusion transgene (Emu-myc) provide a useful model for Burkitt's lymphoma. MATERIALS AND METHODS: Groups of 12 Emu-myc mice were treated prophylactically for 6 weeks after weaning with anti-c-myc DNA phosphorothioate (20 mg/kg/day), scrambled control DNA, or saline, delivered by micro-osmotic pumps. RESULTS: Half of the mice treated with saline or scrambled control DNA displayed palpable tumors by 8-9 weeks after birth, and 95% of them did so by 16 weeks, but 75% of the mice treated with antisense DNA were still free of tumors at the age of 26 weeks. Antisense therapy ablated MYC antigen in the spleens of tumor-bearing mice. Plasma physiological parameters indicated no acute toxicity. CONCLUSIONS: Long-term tumor resistance after anti-c-myc DNA therapy implies induction of a host response. Prophylactic anti-c-myc DNA therapy might prevent lymphoma in asymptomatic individuals displaying c-myc translocations.
