- 积分
- 13286
- 威望
- 13286
- 包包
- 34831
|
本帖最后由 sunsong7 于 2011-6-30 20:27 编辑
% b' L* R( S0 o+ | d2 Z6 j# w; G' C; {! k; l6 V$ i# l2 l
虽然还没有内源性iPS的直接报道,但是体内确实可以实现细胞重编程,相关报道:9 H( |9 v5 @4 @" F; t0 |7 t1 a
( _0 L5 h8 ^- [. u2 G% n+ XDirect in vivo cellular reprogramming involves transition through discrete, non-pluripotent steps 7 W, e5 z; E* o3 @$ W) u- @
Jai Prakash Richard, Steven Zuryn, Nadine Fischer, Valeria Pavet, Nadège Vaucamps and Sophie Jarriault*
- ?. V$ I0 Z2 i& |$ D*Author for correspondence: sophie@igbmc.fr * j ?6 _/ |7 ~/ V5 \ m4 l
DEVELOPMENT AND STEM CELLS Accepted January 31, 2011.
' `, d' a$ t# m- K18th International C. elegans Meeting
- C2 {; t4 q+ y* ~) l
" E. }/ d% P5 M/ c1 Y; l
& y" i% B0 e7 S, p$ q# J! M% ^
( o8 }3 A) S) h( x9 E/ ^In vivo reprogramming of adult pancreatic exocrine cells to bata-cells 8 T# p2 \- P# F/ t
Qiao Zhou1, Juliana Brown2, Andrew Kanarek1, Jayaraj Rajagopal1 & Douglas A. Melton1
# d9 O- x$ l S! h- L! CNature 455, 627-632 (2 October 2008) | doi:10.1038/nature07314; Received 26 June 2008; Accepted 6 August 2008; Published online 27 August 2008
& `* X) M* M* s0 Y* j O9 T5 ^7 f: B* F0 R: o" p$ e: P
Department of Stem Cell and Regenerative Biology, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA 4 J' y2 p( i$ D$ l9 _" }8 n7 x7 m
Department of Pathology, Children's Hospital, Boston, Harvard Medical School, Harvard Stem Cell Institute, 300 Longwood Avenue, Boston, Massachusetts 02115-5724, USA ) g; E& y# R. x5 I7 |
Correspondence to: Douglas A. Melton1 Correspondence and requests for materials should be addressed to D.A.M. (Email: dmelton@harvard.edu).0 t& _; ?, j- l4 h! V
3 k5 s8 Z: a8 F9 g- z9 a
* o2 `/ m5 Y: Y, h& U% p
Top of pageAbstractOne goal of regenerative medicine is to instructively convert adult cells into other cell types for tissue repair and regeneration. Although isolated examples of adult cell reprogramming are known, there is no general understanding of how to turn one cell type into another in a controlled manner. Here, using a strategy of re-expressing key developmental regulators in vivo, we identify a specific combination of three transcription factors (Ngn3 (also known as Neurog3) Pdx1 and Mafa) that reprograms differentiated pancreatic exocrine cells in adult mice into cells that closely resemble -cells. The induced -cells are indistinguishable from endogenous islet -cells in size, shape and ultrastructure. They express genes essential for -cell function and can ameliorate hyperglycaemia by remodelling local vasculature and secreting insulin. This study provides an example of cellular reprogramming using defined factors in an adult organ and suggests a general paradigm for directing cell reprogramming without reversion to a pluripotent stem cell state.
9 d8 M# z8 P; Q- Fhttp://www.nature.com/nature/jou ... bs/nature07314.html0 R ^- m& p3 J. ^5 n
7 u8 @/ q4 Q3 X8 T% h/ ?: h/ e O; F4 w+ J- p* q: i
Methods Mol Biol. 2010;629:307-21.7 g7 X, `% O* I: |
In vivo reprogramming of human telomerase reverse transcriptase (hTERT) by trans-splicing ribozyme to target tumor cells.
c: s* m2 q# C) G1 g" ^Lee SJ, Lee SW, Jeong JS, Kim IH.6 z: L4 m& @8 Q6 Y$ o7 n: `- G. D
SourceGenitourinary Cancer Branch, Research Institute, National Cancer Center, Goyang, Korea.
3 `4 j( A& q( G& J7 ?6 Q: n
# r9 v3 \% p1 c1 `; d* HAbstract
, ^1 }% k8 ]) H: Z1 F) hOur understanding of RNA has evolved over the last 20 years from the initial concept that RNA is simply an intermediate in protein synthesis or a structural component maintaining and expressing genetic information. Subsequently, the non-coding RNAs have attracted huge interest and have been developed as therapeutic reagents as well as research tools. An example of RNA-based therapeutic application is the Tetrahymena group I intron-based trans-splicing ribozyme, which cleaves target RNA and trans-ligates an exon tagged at its 3' end onto the downstream U nucleotide of the targeted RNA. Here, we describe the specific trans-splicing ribozyme that can sense and reprogram human telomerase reverse transcriptase (hTERT)-encoding RNA. This ribozyme converts hTERT RNA to therapeutic transgene herpes simplex virus (HSV) thymidine kinase (tk) and exhibits cytotoxicity to various hTERT-expressing cancer cells. For use in cancer therapy, CMV promoter-driven hTERTRibozyme.HSVtk expression cassette is inserted into adenovirus genome and delivered into either subcutaneous or intraspleenic liver-metastasized xenograft. We present here an evaluation of the inhibitory effects of CMV.hTERTRibozyme.HSVtk on tumor growth.
/ o# @ `+ a! d2 I7 \3 E
" m X: y) T( o2 ?5 Z6 aPMID: 20387158 [PubMed - indexed for MEDLINE]
" h' L" e; C1 n6 p7 E' s) Y6 s! M8 H% T( K Z: I8 z4 ?
http://www.ncbi.nlm.nih.gov/pubmed/20387158- a1 K6 u1 V3 f* v- ^. P. _: d
" Y. {& Y8 J4 {/ K) \In vivo reprogramming of hTERT by trans-splicing ribozyme to target tumor cells.0 ~. c; E- _- Q* C) Q& M" i* H
by Seung-Hee Hong, Jin-Sook Jeong, Yoon-Jong Lee, Haeng-Im Jung, Kyoung-Sook Cho, … Chang-Min Kim, Byung-Su Kwon, Bruce A Sullenger, Seong-Wook Lee, In-Hoo Kim show all authors % ]: y, F$ M9 q; O; }7 W
Molecular therapy the journal of the American Society of Gene Therapy (2008)
0 c( F' [% w3 ^; dVolume: 16, Issue: 1, Pages: 74-808 Y0 |4 g" V Y/ g5 \* a
PubMed: 17700543 4 C- a9 H' n0 d. s" @8 `
Available from www.ncbi.nlm.nih.gov * `" q, T" s) K1 e) r3 b$ ]
2 W6 q. _( D' qAbstract& f! @7 x& T1 L8 X' A. x" g
We have developed and validated a new tumor-targeting gene therapy strategy based upon the targeting and replacement of human telomerase reverse transcriptase (hTERT) RNA, using a trans-splicing ribozyme. By constructing novel adenoviral vectors harboring the hTERT-targeting trans-splicing ribozymes with the downstream reporter gene (Ad-Ribo-LacZ) or suicide gene (Ad-Ribo-HSVtk) driven by the cytomegalovirus (CMV) promoter, we demonstrated that this viral system selectively marks tumor cells expressing hTERT or sensitizes tumor cells to prodrug treatments. We confirmed that Ad-Ribo-LacZ successfully and selectively delivered a ribozyme that performed a highly specific trans-splicing reaction into hTERT-expressing cancer cells, both in vitro and in a peritoneal carcinomatosis nude mouse model. We also determined that the hTERT-specific expression of the suicide gene in the Ad-Ribo-HSVtk, and treatment with the corresponding prodrug, reduced tumor progression with almost the same efficacy as the strong constitutive CMV promoter-driven adenovirus, both in cancer cell lines and in nude mouse HT-29 xenografts. These observations provide the basis for a novel approach to cancer gene therapy, and demonstrate that trans-splicing ribozymes can be employed as targeting anti-cancer agents which recognize cancer-specific transcripts and reprogram them, thereby combating cancerous cells.
' J9 T+ A* J- W5 n( O: r$ s o7 S9 O3 `3 f; n1 L$ ?
; X! b V. O/ M$ u0 _: x8 q
|
附件: 你需要登录才可以下载或查看附件。没有帐号?注册
-
总评分: 威望 + 10
包包 + 20
查看全部评分
|