Strategy for keeping efficient expression and pharmacodynamics in reducing rAAV gene medicine immune response based on the decrease of vector dosage / 药学学报

How to reduce immune response is an unprecedented challenge for rAAV gene medicine. Recent studies suggested that lowering dosage of the vector used could reduce immune response caused by rAAV gene medicine. Nevertheless, it would also decrease the transgene expression, leading to failure of gene treatment. It is therefore important to take appropriate steps to maintain high gene expression level and pharmacodynamic, while the dosage of rAAV used is reduced. Here, steps to enhancing gene therapy, such as optimization of the administration, reconstruction of the viral vector and selection of the promoter, are discussed in order to achieve maximum outcome.

Change of plasma resistin concentration in patients with traumatic brain injury / 中华创伤杂志

Objective To determine plasma resistin level in patients with traumatic brain injury (TBI) and evaluate its correlations with outcome and inflammatory reaction. Methods Fiftyfour patients with moderate TBI, 71 patients with severe TBI and 40 healthy controls were enrolled in this study. Plasma samples were obtained from the healthy controls on physical examination and from the TBI patients on admission. Enzyme-linked immunosorbent assay ( ELISA) was used to determine the plasma resistin concentrations. Results Twenty patients (37.0% ) and 53 patients (74.6% ) with moderate and severe TBI suffered from an unfavorable outcome (defined as GOS score for 1-3 points) three months after TBI respectively. Plasma resistin levels in the patients with moderate and severe TBI were substantially higher than that in the healthy controls ((21. 9 ± 8. 4) ng/ml and (29. 2 ± 9. 6) ng/ml vs (9. 3 ± 2.6) ng/ml, both P ＜0. 01] by using covariance analysis. By using the multivariate linear regression analysis, plasma C-reactive protein level (t =2.212,P =0.035; t =2. 274,P =0. 014) and GCS scores (t =3. 120,P =0.007; t=3.986,P=0.003) were associated with the plasma resistin levels. Logistic regression analysis selected plasma resistin level as an independent predictor for 3-month unfavorable outcome of the patients with moderate and severe TBI (odds ratio = 1. 124, 95% CI = 1. 040-1. 221, P = 0.011; odds ratio = 1. 145, 95% CI = 1. 044-1. 232, P = 0. 009). A receiver operating characteristic curve identified cutoff levels of plasma resistin (22.4 ng/ml and 30.5 ng/ml) that predicted 3-month unfavorable outcome of moderate and severe TBI patients with the high sensitivity (70. 0% and 79. 2% ) and specificity (70.6% and 72.2% ) ( area under curve = 0.719, 95% CI = 0.642-0.829, P = 0.000;area under curve =0.735, 95% CI =0. 671-0. 893, P = 0.000). Conclusions Plasma resistin level is increased after TBI and may be involved in inflammatory response of brain injury. Clinical detection of this indicator can help early determine the prognosis of the TBI patients.

Progress in application of targeting viral vector regulated by microRNA in gene therapy: a review / 生物工程学报

A safe and effective targeting viral vector is the key factor for successful clinical gene therapy. microRNA, a class of small, single-stranded endogenous RNAs, act as post-transcriptional regulators of gene expression. The discovery of these kind regulatory elements provides a new approach to regulate gene expression more accurately. In this review, we elucidated the principle of microRNA in regulation of targeting viral vector. The applications of microRNA in the fields of elimination contamination from replication competent virus, reduction of transgene-specific immunity, promotion of cancer-targeted gene therapy and development of live attenuated vaccines were also discussed.