哈佛医学院Peng Yin和Constance L. Cepko研究组合作研发一种新型FISH技术，可用于细胞和组织中的RNA与DNA复杂成像。2019年6月出版的《Nature Methods》发表了这项成果。

研究人员开发了交换反应信号扩增法（SABER）以实现利用长的单链多联体DNA作为FISH成像探针。这些多联体DNA上聚集了一连串的短的荧光成像互补序列。利用SABER法可以将固定的细胞和组织中RNA与DNA的信号增强5-450倍。此外，研究人员利用17个正交探针实现同时对染色质多个靶点的成像与高效检测。研究人员进一步用该技术实现了小鼠视网膜中具有不同细胞类型活性的增强子检测。因此，SABER技术展示出其在核酸靶点进行快速、经济地复杂成像具有简便性与多功能性。

据了解，荧光原位杂交（FISH）技术能够在固定样本中显示核酸序列的丰度与定位。尽管最近FISH信号的复杂扩增方面取得了进展，但是如何以高效率、简易的流程来实现同步扩增和分步检测仍然具有挑战性。

附：英文原文

Title: SABER amplifies FISH: enhanced multiplexed imaging of RNA and DNA in cells and tissues

Author: Jocelyn Y. Kishi, Sylvain W. Lapan, Brian J. Beliveau, Emma R. West, Allen Zhu, Hiroshi M. Sasaki, Sinem K. Saka, Yu Wang, Constance L. Cepko, Peng Yin

Issue&Volume: Volume 16 Issue 6, June 2019

Abstract: Fluorescence in situ hybridization (FISH) reveals the abundance and positioning of nucleic acid sequences in fixed samples. Despite recent advances in multiplexed amplification of FISH signals, it remains challenging to achieve high levels of simultaneous amplification and sequential detection with high sampling efficiency and simple workflows. Here we introduce signal amplification by exchange reaction (SABER), which endows oligonucleotide-based FISH probes with long, single-stranded DNA concatemers that aggregate a multitude of short complementary fluorescent imager strands. We show that SABER amplified RNA and DNA FISH signals (5- to 450-fold) in fixed cells and tissues. We also applied 17 orthogonal amplifiers against chromosomal targets simultaneously and detected mRNAs with high efficiency. We then used 10-plex SABER-FISH to identify in vivo introduced enhancers with cell-type-specific activity in the mouse retina. SABER represents a simple and versatile molecular toolkit for rapid and cost-effective multiplexed imaging of nucleic acid targets.

DOI: 10.1038/s41592-019-0404-0

Source:https://www.nature.com/articles/s41592-019-0404-0