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本帖最后由 StephenW 于 2014-10-7 20:09 编辑
10th Annual Meeting of the Oligonucleotide Therapeutics Society
Session 10: Preclinical/Clinical III
Andrew Vaillant
Wednesday, October 15, 2014 4:30PM-4:45PM
Nucleic Acid Polymers for the Treatment of Chronic HBV:A new therapeutic alternative.
Andrew Vaillant
REPLICor Inc., Montreal, Canada
The hepatitis B surface antigen (HBsAg) is an immuno-inhibitory protein released from infected hepatocytes and the abundant circulating levels of this protein play a key role in the chronic suppression of the immune response and maintenance of HBV infection. Nucleic acid polymers (NAPs) use the sequence independent and size dependent properties of phosphorothioate oligonucleotides to target amphipathic interactions critical for the release of hepatitis B surface antigen from infected hepatocytes. Unlike antisense or siRNA strategies which target viral sequences, the interaction between NAPs and their target is insensitive to viral mutation. NAPs naturally accumulate in the liver and can be further optimized to remove immunostimulatory, hybridization and aptameric off target effects. The use of two such optimized NAPs (REP 2055 and REP 2139) in human patients are well tolerated and reliably remove circulating HBsAg (up to 5 log reductions) to undetectable levels in patients, resulting in the appearance of anti-HBsAg antibodies, elimination of HBeAg, the appearance of anti-HBeAg antibodies and 3–9 log reductions in viral titers. Despite the complete removal of HBsAg and HBeAg for several months, only 25% of patients achieved SVR off treatment (HBV DNA < 20 copies / ml). Combination therapy with NAPs and immunotherapy was well tolerated and improved the speed of the antiviral response and lead to 89% of patients achieving SVR off treatment. These results demonstrate that prolonged elimination of viral antigens is insufficient to elicit SVR in most patients with chronic HBV infection and that concomitant immunotherapy is required to re-establish immune control in the absence of viral antigens in most patients. NAPs represent an alternative application of oligonucleotide chemistry which will provide an important new advance for HBV therapy.
Andrew Vaillant, Ph.D.
Chief Scientific Officer
REPLICor Inc.
6100 Royalmount Avenue
Montreal, Quebec H4P 2R2
Canada
[email protected]
寡核苷酸治疗学会第10届年会
第10节：临床前/临床III
安德鲁·威能
周三，2014年10月15日下午4点半，下午4时45分
核酸聚合物用于慢性乙肝的治疗：一种新的治疗选择。
安德鲁·威能
REPLICor公司，加拿大蒙特利尔B型肝炎表面抗原（HBsAg）是从感染的肝细胞和该蛋白质的丰富的循环水平释放在HBV感染的免疫应答和维护的慢性抑制中发挥关键作用的免疫抑制性蛋白。核酸聚合物（行动方案）使用硫代磷酸酯寡核苷酸的序列独立和尺寸依赖特性为目标对乙型肝炎表面抗原的来自感染的肝细胞中释放临界两亲性的相互作用。不同于反义或siRNA的策略靶向的病毒序列，NAP和其目标之间的相互作用是不敏感的病毒的突变。行动方案自然地积聚在肝脏中，并且可以被进一步优化以除去免疫，杂交和aptameric脱靶效应。使用在人类患者中两个这样的优化行动方案（REP2055和REP2139）的耐受性良好且可靠地除去循环的HBsAg（最多5数减少）到检测不到的水平的患者，产生抗HBsAg的外观抗体，消除HBeAg，抗-HBeAg的抗体和3的外观的-9日志减少病毒滴度。尽管彻底清除HBsAg和HBeAg的几个月中，只有25％的患者获得SVR关闭处理（HBV DNA<20拷贝/毫升）。联合治疗与NAP和免疫耐受良好的和改进的抗病毒反应的速度，并导致患者实现SVR断治疗89％。这些结果证明，长时间消除病毒抗原不足以引起SVR中最慢性HBV感染和随之而来的免疫疗法，需要重新建立免疫控制在不存在病毒抗原在大多数患者。国家行动计划表示寡核苷酸化学的另一种应用程序，它会为乙肝治疗的一个新的重要进展。
安德鲁·威能，博士
首席科学官
REPLICor公司
6100 Royalmount大道
蒙特利尔，魁北克H4P2R2
加拿大
[email protected]
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发表于 2014-10-7 20:08
很迷茫呀