梁子才
研究主要集中在核酸手段在生物医学研究和转化方面的应用, 其中包括:1)RNA干扰相关的基础研究:包括RNA干扰的机制,microRNA,non-coding RNA的研究方法及其功能。2)RNA干扰的应用基础研究,包括siRNA载体,文库及其筛选应用。3)RNA干扰的制药应用:核酸化学发展、RNA干扰的在体研究、针对疾病的siRNA筛选和制药研究。4)创新呔库和膜蛋白的相互作用。
个性化签名
- 姓名:梁子才
- 目前身份:
- 担任导师情况:
- 学位:
-
学术头衔:
“973”、“863”首席科学家, 博士生导师
- 职称:-
-
学科领域:
生物化学
- 研究兴趣:研究主要集中在核酸手段在生物医学研究和转化方面的应用, 其中包括:1)RNA干扰相关的基础研究:包括RNA干扰的机制,microRNA,non-coding RNA的研究方法及其功能。2)RNA干扰的应用基础研究,包括siRNA载体,文库及其筛选应用。3)RNA干扰的制药应用:核酸化学发展、RNA干扰的在体研究、针对疾病的siRNA筛选和制药研究。4)创新呔库和膜蛋白的相互作用。
梁子才 教授
Ph.D., 博士生导师
核酸技术研究室主任
分子医学研究所教育委员会主任
教育背景:1981-1985 南开大学生物系,获学士学位;1985-1988 南开大学生物系,获硕士学位;1990-1995 瑞典乌普萨拉大学(Uppsala University),获博士学位。
研究经历:1988-1990 中国科学院动物研究所,实习研究员;1995-1998 美国耶鲁大学生化生物物理学系,从事博士后研究;1998-2005 瑞典卡珞琳斯卡医学院基因组与生物信息学中心基因组技术研究室主任, 助教授,副教授;2006至今 北京大学分子医学研究所教授,博士生导师,核酸技术研究室主任。
其他学术兼职:2000-2002 瑞典卡珞琳斯卡医学院核酸芯片中心实验室兼职主任;2002-2005 中国国家人类基因组北方研究中心分子生物学兼职教授,第一个siRNA国家863重点项目的主持人;2006至今 瑞典卡珞琳斯卡医学院分子医学和外科系兼职研究员(Adjunct Researcher)。2001-2004年度“世界市场报告:未来药物开发商务简讯”顾问 (advisor, Annual World Markets report: Business Briefing - Future Drug Development );2005至今 Journal of RNAi and Gene Silencing杂志编委;2007年7月中法心血管分子医学论坛组委会秘书长;2008年4月 第一届中国小核酸技术与应用学术会议(RNAi China,2008)筹备人,组委会秘书长。
从1998年起,梁子才教授作为 研究室主任(PI)从事基因组技术这一交叉前沿领域的研究,取得了多项创新成果:建立了一系列有自主知识产权的生物技术平台。其中包括:1)两种DNA芯片的新方法的建立;2)利用DNA随机库进行mRNA对反义核酸可近性的研究;3) siRNA载体系统和siRNA评价系统,并形成了覆盖大量已知基因的siRNA库及全随机siRNA库等重要技术平台;在利用各种siRNA库进行功能基因筛选方面取得创新成果;RNA干扰特异性研究得到RNA中A:C配对的重要发现;4)在利用DNA随机库进行功能多肽研究方面建立全新的方法。提交专利申请10项,其中5项为PCT申请。
梁子才教授目前的研究主要集中在核酸手段在生物医学研究和转化方面的应用, 其中包括:1)RNA干扰相关的基础研究:包括RNA干扰的机制,microRNA,non-coding RNA的研究方法及其功能。2)RNA干扰的应用基础研究,包括siRNA载体,文库及其筛选应用。3)RNA干扰的制药应用:核酸化学发展、RNA干扰的在体研究、针对疾病的siRNA筛选和制药研究。4)创新呔库和膜蛋白的相互作用。
-
主页访问
2094
-
关注数
0
-
成果阅读
457
-
成果数
13
【期刊论文】Analysis of siRNA specificity on targets with double-nucleotide mismatches
梁子才, Cecilia Dahlgren, *, Hong-Yan Zhang, Quan Du, Maria Grahn, Gunnar Norstedt, Claes Wahlestedt and Zicai Liang,
Nucleic Acids Research, 2008, Vol. 36, No.9 e53,-0001,():
-1年11月30日
Although RNA interference as a tool for gene knockdown is a great promise for future applications, the specificity of small interfering RNA (siRNA)-mediated gene silencing needs to be thoroughly investigated. Most research regarding siRNA specificity has involved analysis of affected off-target genes instead of exploring the specificity of the siRNA itself. In this study we have developed an efficient method for generating a siRNA target library by combining a siRNA target validation vector with a nucleotide oligomix. We have used this library to perform an analysis of the silencing effects of a functional siRNA towards its target site with double-nucleotide mismatches. The results indicated that not only the positions of the mismatched base pair have an impact on silencing efficiency but also the identity of the mismatched nucleotide. Our data strengthen earlier observations of widespread siRNA off-target effects and shows that 35% of the double-mutated target sites still causes knockdown efficiency of >50%. We also provide evidence that there may be substantial differences in knockdown efficiency depending on whether the mutations are positioned within the siRNA itself or in the corresponding target site.
-
37浏览
-
0点赞
-
0收藏
-
0分享
-
116下载
-
0评论
-
引用
梁子才, Yongzhen Gao, Lilian Sun, Jie Dong, Xingye Xu, Yuelong Shu, Meihong Chen, Li Yin, Zicai Liang, , * and Qi Jin*
Antiviral Therapy 11: 431-438,-0001,():
-1年11月30日
-
32浏览
-
0点赞
-
0收藏
-
0分享
-
91下载
-
0评论
-
引用
【期刊论文】Vector-based siRNA delivery strategies for high-throughput screening of novel target genes
梁子才, Meihong Chen, Quan Du, Hong-Yan Zhang, Claes Wahlestedt, and Zicai Liang*
Journal of RNAi and Gene Silencing (2005), 1(1), 5-11,-0001,():
-1年11月30日
Application of siRNA in high-throughput fashion is still in its early phase although the principle has been established for three years. In this review, we outline the different vector-based siRNA delivery platforms as well as resources that are becoming available for high-throughput applications, and some initial outcomes of vector siRNA high-throughput screening efforts using vector encoded siRNA. It is expected that further improvement of the siRNA technology and availability of the siRNA resources will help to materialize the potential of siRNA for functional genomics and drug target validation.
siRNA, RNAi, vectors, gene silencing, siRNA delivery
-
40浏览
-
0点赞
-
0收藏
-
0分享
-
123下载
-
0评论
-
引用
梁子才, Quan Du*, Håkan Thonberg, Jue Wang, Claes Wahlestedt and Zicai Liang
Nucleic Acids Research, 2005, Vol. 33, No.5 1671-1677,-0001,():
-1年11月30日
The specificity of small interfering RNA (siRNA)-mediated gene silencing is a critical consideration for the application of RNA interference (RNAi). While the discovery of potential off-target effects by siRNAs is of concern, no systematic analysis has been conducted to explore the specificity of RNAi. Here, we present a study where a functionally validated siRNA (siCD46) was examined for silencing specificityonall possible 57 permutated target sites, each carrying a single-nucleotide mutation that would generate a mismatch when paired with siRNA antisense strand. We found that it was not only the position of the mismatched base pair, but also the identity of the nucleotides forming the mismatch that influenced silencing. Surprisingly, mismatches formed between adenine (A) and cytosine (C), in addition to the G:U wobble base pair, were well tolerated and target sites containing such mismatches were silenced almost as efficiently as its fully matched counterpart by siCD46. Northern blots showed that the silencing of fusion genes harboring the mutated target sites involved target mRNA degradation. This study provides direct evidence that the target recognition of siRNA is far more degenerative than previously considered. This finding is instrumental in the understanding of RNAi specificity and may aid the computational prediction of RNA secondary structure.
-
47浏览
-
0点赞
-
0收藏
-
0分享
-
100下载
-
0评论
-
引用
【期刊论文】Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality
梁子才, Joacim Elmen*, Hakan Thonberg, Karl Ljungberg, Miriam Frieden, Majken Westergaard, Yunhe Xu, Britta Wahren, Zicai Liang, Henrik Ørum, Troels Koch and Claes Wahlestedt
Nucleic Acids Research, 2005, Vol. 33, No.1 439-447,-0001,():
-1年11月30日
Therapeutic application of the recently discovered small interfering RNA (siRNA) gene silencing phenomenon will be dependent on improvements in molecule bio-stability, specificity and delivery. To address these issues, we have systematically modified siRNA with the synthetic RNA-like high affinity nucleotide analogue, Locked Nucleic Acid (LNA). Here,weshowthat incorporation of LNAsubstantially enhances serum half-life of siRNA’s, which is a key requirement for therapeutic use. Moreover, we provide evidence that LNA is compatible with the intracellular siRNA machinery and can be used to reduce undesired, sequence-related off-target effects. LNA-modified siRNAs targeting the emerging disease SARS, show improved efficiency over unmodified siRNA on certain RNA motifs. The results from this study emphasize LNA’s promise in converting siRNA from a functional genomics technology to a therapeutic platform.
-
61浏览
-
0点赞
-
0收藏
-
0分享
-
131下载
-
0评论
-
引用
【期刊论文】A universal plasmid library encoding all permutations of small interfering RNA
梁子才, Meihong Chen*†‡, Lishu Zhang*†‡, Hong-Yan Zhang‡§, Xiahui Xiong*†, Bo Wang*†, Quan Du§, Bing Lu*, Claes Wahlestedt§¶, and Zicai Liang*
PNAS February 15, 2005 vol. 102 no.7,-0001,():
-1年11月30日
Small interfering RNA (siRNA) is normally designed to silence preselected known genes. Such selections are inevitably prone to bias as a result of limited knowledge about the biological process, transcript identity, and functions. A library that contains all permutations of siRNA could avoid such problems. In this paper, it is shown that 5×107 siRNA-encoding plasmids can be constructed in a single tube by using vectors with two mutated RNA polymerase III promoters arranged in a convergent manner. Such a library was used to carry out genomewide screening of functional genes in a phenotype-driven manner. Multiple siRNAs that induce a significant increase of cell proliferation speed were identified.
random targeting, screening, vector, dual promoters
-
27浏览
-
0点赞
-
0收藏
-
0分享
-
48下载
-
0评论
-
引用
梁子才, Joacim Elména, *, Hong-Yan Zhanga, Bartek Zuberb, Karl Ljungbergb, Britta Wahrenb, Claes Wahlestedta, Zicai Lianga
FEBS Letters 578(2004)285-290,-0001,():
-1年11月30日
We have evaluated antisense design and efficacy of locked nucleic acid (LNA) and DNA oligonucleotide (ON) mix-mers targeting the conserved HIV-1 dimerization initiation site (DIS). LNA is a high affinity nucleotide analog, nuclease resistant and elicits minimal toxicity. We show that inclusion of LNA bases in antisense ONs augments the interference of HIV-1 genome dimerization. We also demonstrate the concomitant RNase H activation by six consecutive DNA bases in an LNA/DNA mix-mer. We show ON uptake via receptor-mediated transfection of a human T-cell line in which the mix-mers subsequently inhibit replication of a clinical HIV-1 isolate. Thus, the technique of LNA/DNA mix-mer antisense ONs targeting the conserved HIV-1 DIS region may provide a strategy to prevent HIV-1 assembly in the clinic.
LNA, Antisense, RNase H, HIV, Dimerization initiation site
-
31浏览
-
0点赞
-
0收藏
-
0分享
-
62下载
-
0评论
-
引用
【期刊论文】Validating siRNA using a reporter made from synthetic DNA oligonucleotides
梁子才, Quan Du, Ha˚kan Thonberg, Hong-Yan Zhang, Claes Wahlestedt, Zicai Liang*
Biochemical and Biophysical Research Communications 325(2004)243-249,-0001,():
-1年11月30日
Only a small fraction of all siRNAs are effective in silencing their target genes, and siRNA efficacy can only be determined experimentally. Previously described reporter-based siRNA validation methods all rely on the availability of physical cDNA clones, and this limits the high throughput applicability of the method. In the current report, we used short synthetic DNA fragment containing a siRNA targeting site, instead of cDNA, to fuse with a reporter gene. When targeting such transcripts with different siRNAs, we found that such constructs can faithfully report the efficacy of the corresponding siRNAs in a sequence specific manner, even when the inserted DNA fragment is essentially only long enough to cover the targeting site. The efficacy of both vector-based siRNA and synthetic siRNA can be evaluated using this system. Since only readily available short synthetic DNA fragments are needed for forming the evaluation vector, this method provides an appealing way of validating siRNAs in high throughput.
siRNA, Target site, Dual-luciferase assay, Efficacy validation, Reporter, Oligonucleotides
-
33浏览
-
0点赞
-
0收藏
-
0分享
-
89下载
-
0评论
-
引用
【期刊论文】Functional comparison of single-and double-stranded siRNAs in mammalian cells
梁子才, Yunhe Xu, a, b, c, * Annika Linde, c Ola Larsson, a Dorit Thormeyer, a Joacim Elmen, a Claes Wahlestedt, a and Zicai Lianga, *
Biochemical and Biophysical Research Communications 316(2004)680-687,-0001,():
-1年11月30日
The concept of small interfering RNA (siRNA) has been extended to include not only short double-stranded RNA of 19-25 bp, but also single-stranded antisense RNA of the same length, since such single-stranded antisense siRNAs were recently found to be able to inhibit gene expression as well. We made comprehensive comparison of double- and single-stranded siRNA functions in RNA interference (RNAi), targeting multiple sites and different mRNAs, measuring RNAi effects at different time-points and in different cell lines, and examining response curves. Duplex siRNAs were found to be more potent than single-stranded antisense siRNAs. This was verified by the observation that single-stranded antisense siRNAs, which were inefficient in some cases when used alone, could be rescued from inefficiency by sequentially transfecting with the sense siRNAs. This result suggests that the structural character of siRNA molecules might be a more important determinant of siRNA efficiency than the cellular persistence of them.
RNA interference, Small interfering RNA, Cultured mammalian cells, CD46
-
24浏览
-
0点赞
-
0收藏
-
0分享
-
48下载
-
0评论
-
引用
梁子才, Yunhe Xu, Hong-Yan Zhang, Dorit Thormeyer, Ola Larsson, Quan Du, Joacim Elmen, Claes Wahlestedt, and Zicai Liang*
Biochemical and Biophysical Research Communications 306(2003)712-717,-0001,():
-1年11月30日
Antisense DNA target sites can be selected by the accessibility of the mRNA target. It remains unknown whether a mRNA site that is accessible to an antisense DNA is also a good candidate target site for a siRNA. Here, we reported a parallel analysis of 12 pairs of antisense DNAs and siRNA duplexes for their potency to inhibit reporter luciferase activity in mammalian cells, both of the antisense DNA and siRNA agents in a pair being directed to same site in the mRNA. Five siRNAs and two antisense DNAs turned out to be effective, but the sites targeted by those effective siRNAs and antisense DNAs did not overlap. Our results indicated that effective antisense DNAs and siRNAs have different preferences for target sites in the mRNA.
Small interfering RNAs, Antisense DNAs, mRNA
-
33浏览
-
0点赞
-
0收藏
-
0分享
-
65下载
-
0评论
-
引用