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文章數：72 |
 一笈壽司上餐速度快嗎？》公益路10家必訪餐廳｜吃貨必備指南 |
| 創作｜散文 2026/04/21 04:05:52 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
身為一個熱愛美食、喜歡在城市裡挖掘驚喜的人，臺中公益路一直是我最常出沒的地方之一。這條路可說是「臺中人的美食戰場」，從精緻西餐到創意火鍋，從日式丼飯到義式早午餐，每走幾步，就會有完全不同的特色料理餐廳。 這次我特別花了一整個月，實際造訪了公益路上十間口碑不錯的餐廳。有的是網友熱推的打卡名店，也有隱藏在巷弄裡的小驚喜。我以環境氛圍、口味表現、價格CP值與再訪意願為基準，整理出這篇實測評比。希望能幫正在猶豫去哪裡吃飯的你，找到那一間「吃完會想再來」的餐廳。 評比標準與整理方向
這次我走訪的10家餐廳橫跨不同料理類型，從高質感牛排館到巷弄系早午餐，每一間都有自己獨特的風格。為了讓整體比較更客觀，我依照以下四大面向進行評比，並搭配實際用餐體驗來打分。
整體而言，我希望這份評比不只是「哪家好吃」，而是幫你在不同情境下（約會、家庭聚餐、朋友小聚、商業午餐）都能快速找到合適的選擇。畢竟，美食不只是味覺的滿足，更是一段段與朋友共享的生活記憶。 10間臺中公益路餐廳評比懶人包公益路向來是臺中人聚餐的首選地段，從火鍋、燒肉到中式料理與早午餐，每走幾步就有驚喜。以下是我實際造訪過的10間代表性餐廳清單，橫跨平價、創意、高級各路風格。
一頭牛日式燒肉｜炭香濃郁的和牛饗宴，約會聚餐首選
走在公益路上，很難不被 一頭牛日式燒肉 的木質外觀吸引。低調卻不失質感的門面，搭配昏黃燈光與暖色調的內裝，讓人一進門就感受到濃濃的日式職人氛圍。店內空間不大，但桌距規劃得宜，每桌皆設有獨立排煙設備，烤肉時完全不怕滿身油煙味。 餐點特色
一頭牛的靈魂，絕對是他們招牌的「三國和牛拼盤」。 用餐體驗整體節奏掌握得非常好。店員會在你剛想烤下一片肉時貼心遞上夾子、幫忙換烤網，讓人完全不用分心。整場用餐過程就像一場表演，從視覺、嗅覺到味覺都被滿足。 綜合評分
地址：408臺中市南屯區公益路二段162號電話：04-23206800 小結語一頭牛日式燒肉不僅是「吃肉的地方」，更像是一場五感盛宴。從進門那一刻到最後一道甜點，都能感受到他們對細節的用心。 TANG Zhan 湯棧｜文青系火鍋代表，麻香湯底與視覺美感並重
在公益路這條美食戰線上，TANG Zhan 湯棧 是讓人一眼就會想走進去的那一種。 餐點特色
湯棧最有名的當然是它的「麻香鍋」。 用餐體驗整體氛圍比一般火鍋店更有質感。 綜合評分
地址：408臺中市南屯區公益路二段248號電話：04-22580617 官網：https://www.facebook.com/TangZhan.tw/ 小結語TANG Zhan 湯棧 把傳統火鍋做出新的樣貌保留臺式鍋物的溫度，又結合現代風格與細節服務，讓吃鍋這件事變得更有品味。 如果你想找一間兼具「好吃、好拍、好放鬆」的火鍋店，湯棧會是公益路上最有風格的選擇之一。 NINI 尼尼臺中店｜明亮寬敞的義式早午餐天堂
如果說前兩間是肉食愛好者的天堂，那 NINI 尼尼臺中店 絕對是想放鬆、聊聊天的好地方。餐廳外觀以白色系與大片玻璃窗為主，陽光灑進室內，讓人一踏入就有種度假般的輕盈感。假日早午餐時段特別熱鬧，建議提早訂位。 餐點特色
NINI 的菜單融合義式與臺灣人口味，選擇多樣且份量十足。主打的 松露燉飯 濃郁卻不膩口，米芯保留微Q口感；而 香蒜海鮮義大利麵 則以新鮮白蝦、花枝與淡菜搭配微辣蒜香，口感層次豐富。 用餐體驗店內氣氛輕鬆不拘謹，無論是一個人帶電腦工作、或朋友聚餐，都能找到舒服角落。餐點上桌速度穩定，服務人員態度親切、補水與收盤都非常主動。整體節奏讓人覺得「時間變慢了」，很適合想遠離忙碌日常的人。 綜合評分
地址：40861臺中市南屯區公益路二段18號電話：04-23288498 小結語NINI 尼尼臺中店是一間能讓人放下手機、慢慢吃飯的餐廳。餐點不追求浮誇，而是以「剛剛好」的份量與風味，陪伴每個平凡午後。如果你在找一間能邊吃邊聊天、拍照也漂亮的早午餐店，NINI 會是你在公益路上最不費力的幸福選擇。 加分100%浜中特選昆布鍋物｜平價卻用心的湯頭系火鍋，家庭聚餐好選擇
在公益路這條高質感餐廳林立的戰場上，加分100%浜中特選昆布鍋物 走的是截然不同的路線。它沒有浮誇的裝潢、也沒有高價位的套餐，但靠著實在的湯頭與親切的服務，默默吸引許多回頭客。每到用餐時間，總能看到家庭或情侶三兩成群地圍著鍋邊聊天。 餐點特色
主打 北海道浜中昆布湯底，湯頭清澈卻不單薄，越煮越能喝出海藻與柴魚的自然香氣。 用餐體驗整體氛圍偏家庭取向，桌距寬敞、座位舒適，帶小孩來也不覺擁擠。店員態度親切，補湯、收盤都很勤快，給人一種「被照顧著」的安心感。 綜合評分
地址：403臺中市西區公益路288號電話：0910855180 小結語加分100%浜中特選昆布鍋物是一間「不浮誇、但會讓人想再訪」的火鍋店。它不追求豪華擺盤，而是用最簡單的湯頭與新鮮食材，傳遞出家常卻不平凡的溫度。 印月餐廳｜中式料理的藝術演繹，宴客與家庭聚會首選
說到臺中公益路的中式料理代表，印月餐廳 絕對是榜上有名。這間開業多年的餐廳以「中菜西吃」的概念聞名，把傳統中式料理以現代手法重新詮釋。從建築外觀到餐具擺設，每個細節都散發著低調的典雅氣息。 餐點特色
印月最令人印象深刻的是他們將傳統中菜融入創意手法。 用餐體驗服務方面完全對得起餐廳的高級定位。從入座、點餐到上菜節奏，都拿捏得恰如其分。每道菜都會有服務人員細心介紹食材與吃法，讓人感受到「被款待」的尊榮感。 綜合評分
地址：408臺中市南屯區公益路二段818號電話：0422511155 小結語印月餐廳是一間「不只吃飯，更像品味生活」的地方。 KoDō 和牛燒肉｜極致職人精神，專為儀式感與頂級味覺而生
若要形容 KoDō 和牛燒肉 的用餐體驗，一句話足以總結——「像在欣賞一場關於肉的表演」。 餐點特色
這裡主打 日本A5和牛冷藏肉，以「精切厚燒」的方式呈現。 用餐體驗KoDō 的最大特色是「儀式感」。 綜合評分
地址：403臺中市西區公益路260號電話：0423220312 官網：https://www.facebook.com/kodo2018/ 小結語KoDō 和牛燒肉不是日常餐廳，而是一場體驗。 永心鳳茶｜在茶香裡用餐的優雅時光，臺味早午餐的新詮釋
走進 永心鳳茶公益店，彷彿進入一間有氣質的茶館。 餐點特色
永心鳳茶的餐點結合中式靈魂與西式擺盤，無論是「炸雞腿飯」還是「紅玉紅茶拿鐵」，都能讓人感受到熟悉卻不平凡的味道。 用餐體驗店內服務人員態度溫和，對茶品介紹詳盡。上餐節奏剛好，不急不徐。 綜合評分
地址：40360臺中市西區公益路68號三樓(勤美誠品)電話：0423221118 小結語永心鳳茶讓人重新定義「臺味」。 三希樓｜老饕級江浙功夫菜，穩重又帶人情味的中式饗宴
位於公益路上的 三希樓 是許多臺中老饕的口袋名單。 餐點特色
三希樓的菜色以 江浙與港式料理 為主，兼顧傳統與現代風味。 用餐體驗三希樓的服務給人一種老派但貼心的感覺。 綜合評分
地址：408臺中市南屯區公益路二段95號電話：0423202322 官網：https://www.sanxilou.com.tw/ 小結語三希樓是一間「吃得出功夫」的餐廳。 一笈壽司｜低調奢華的無菜單日料，職人手藝詮釋旬味極致
在熱鬧的公益路上，一笈壽司 低調得幾乎不顯眼。 餐點特色
一笈壽司採 Omakase（無菜單料理） 形式，每一餐都由主廚根據當日食材設計。 用餐體驗整場用餐約90分鐘，節奏緩慢但沉穩。 綜合評分
地址：408臺中市南屯區公益路二段25號電話：0423206368 官網：https://www.facebook.com/YIJI.sushi/ 小結語一笈壽司是一間真正讓人「放慢呼吸」的餐廳。 茶六燒肉堂｜人氣爆棚的和牛燒肉聖地，肉香與幸福感同時滿分
若要票選公益路上「最難訂位」的餐廳，茶六燒肉堂 絕對名列前茅。 餐點特色
茶六主打 和牛燒肉套餐，價格約落在 $700–$1000 間，份量與品質兼具。 用餐體驗茶六的服務效率相當高。店員親切、換網勤快、補水速度快，整場用餐流程流暢無壓力。 綜合評分
地址：403臺中市西區公益路268號電話：0423281167 官網：https://inline.app/booking/-L93VSXuz8o86ahWDRg0:inline-live-karuizawa/-LUYUEIOYwa7GCUpAFWA 小結語茶六燒肉堂用「穩定品質＋輕奢氛圍」抓住了臺中年輕族群的心。 吃完10家公益路餐廳後的心得與結語吃完這十家餐廳後，臺中公益路不只是一條美食街，而是一段生活風景線。 有的餐廳講究細膩與儀式感，像 一頭牛日式燒肉 與 一笈壽司，讓人感受到食材最純粹的美好 有的則以親切與溫度打動人心，像 加分昆布鍋物、永心鳳茶，讓人明白吃飯不只是為了飽足，而是一種被照顧的幸福。 而像茶六燒肉堂、TANG Zhan 湯棧 這類人氣名店，則用穩定的品質與熱絡的氛圍，成為許多臺中人心中「想吃肉就去那裡」的代名詞。 這十家店，構成了公益路最動人的縮影 有華麗的，也有溫柔的；有傳統的，也有創新的。 每一家都在自己的風格裡發光，讓人吃到的不只是料理，而是一種生活的溫度與節奏。 對我而言，這不僅是一場美食旅程，更是一趟關於「臺中味道」的回憶之旅。 FAQ：關於臺中公益路美食常見問題Q1：公益路哪一區的餐廳最集中？ Q2：需要提前訂位嗎？ 最後的話若要用一句話形容這趟美食之旅，我會說： NINI 尼尼臺中店尾牙聚餐表現如何？ 如果你也和我一樣喜歡用味蕾探索一座城市，那就把這篇公益路美食攻略收藏起來吧。KoDō 和牛燒肉小資族值得嗎？ 無論是約會、慶生、家庭聚餐，或只是想犒賞一下辛苦的自己——這條路上永遠會有一間剛剛好的餐廳在等你。NINI 尼尼臺中店需要訂位嗎？ 下一餐，不妨從這10家開始。一頭牛日式燒肉情侶來合適嗎？ 打開手機、約上朋友，讓公益路成為你生活裡最容易抵達的小確幸。三希樓慶生氛圍夠嗎？ 如果你有私心愛店，也歡迎留言分享，加分100%浜中特選昆布鍋物人潮很多嗎？ 你的推薦，可能讓我下一趟美食旅程變得更精彩。KoDō 和牛燒肉上餐速度快嗎？ Scientists have gained gained deeper insights into cell degradation and recycling processes, known as autophagy. This research provides insights into the link between autophagy and age-related diseases like cancer and neurological disorders. Findings may have important implications for understanding age-related diseases. Scientists at Sanford Burnham Prebys have gained a deeper insight into the intricacies of autophagy, the process in which cells degrade and recycle cellular components. The findings, published in Current Biology, describe how the “trash bags” in a cell — called autophagosomes — are tagged to direct their movement to the cellular “recycling plants” where waste is processed. The research opens new paths to understanding the relationship between autophagy and age-related diseases such as cancer and neurological disorders. “Our latest study identifies how a chemical modification (phosphate-related tag) of a key autophagosome component, the protein called LCB3, helps direct the transport of autophagosomes within the cell in the right direction,” says Malene Hansen, Ph.D., professor at Sanford Burnham Prebys and senior author of the study. “We previously reported that LCB3, which is found on the surface of autophagosomes, needs to be tagged for autophagy to function effectively. Now we have a better understanding of how tagging happens and how important it is for autophagosome movement.” In addition to their own laboratory studies, the Hansen lab worked with colleagues in the lab of Sandra Encalada, Ph.D., at the Scripps Research Institute, San Diego, leaders in the field of transport of cellular components in neurons. Those investigations showed that blocking the chemical modification of the LC3B protein disrupted the efficient transport of autophagosomes toward the cellular recycling plants. Malene Hansen, Ph.D., and Jose Luis Nieto-Torres, Ph.D. Credit: Sanford Burnham Prebys “Waste transport in a cell is like moving garbage trucks down a highway,” says Jose Luis Nieto-Torres, Ph.D., a postdoc in the Hansen laboratory and first author of the study. “Together with our collaborators, we studied the process in nerve cells because they are long and flat, which helps us observe the directional aspects of transport, a critical aspect for waste recycling via autophagy. “We clearly saw that if phosphate tagging of LC3B was hampered, autophagosomes, or the trash bags filled with waste, failed to move in the direction of lysosomes — cell’s recycling plant. This is potentially very harmful to the health of a cell. It’s somewhat analogous to what would happen if a garbage truck didn’t pick up your trash — your waste could accumulate, become scattered in the neighborhood and create a health hazard.” As a next step, the researchers want to figure out which waste products are selected for recycling and how a cell determines when to start moving the waste. “My lab’s research efforts are focused on the relationship between aging and autophagy,” concludes Hansen. “Based on this discovery, we have a new, potential entry point to modulate the activity of recycling in a cell, which may prove relevant to understanding the diminished functions of autophagy that are known to occur in aging cells. Such insights could ultimately lead to new drug targets to combat age-related diseases as well as potential diagnostic markers to assess autophagy ‘health,’ an important goal for the future.” Reference: “LC3B phosphorylation regulates FYCO1 binding and directional transport of autophagosomes” by Jose L. Nieto-Torres, Sean-Luc Shanahan, Romain Chassefeyre, Tai Chaiamarit, Sviatlana Zaretski, Sara Landeras-Bueno, Adriaan Verhelle, Sandra E. Encalada and Malene Hansen, 18 June 2021, Current Biology. DOI: 10.1016/j.cub.2021.05.052 Additional study authors include Sean-Luc Shanahan and Sviatlana Zaretski at Sanford Burnham Prebys; and Romain Chassefeyre, Tai Chaiamarit, Sara Landeras-Bueno, Adriaan Verhelle and Sandra E. Encalada at Scripps Research. This research was supported by funding to Jose L. Nieto-Torres by a Fundacion Ramon Areces Postdoctoral Fellowship and a K99/R00 pathway to independence National Institutes of Health (NIH) grant (K99AG062774); Romain Chassefeyre was supported by the George E. Hewitt Foundation for Medical Research; and Tai Chaiamarit was supported by a Royal Thai Government Scholarship from the Development and Promotion of Science and Technology Talents Project. This work was also funded by grants to Sandra E. Encalada: an NIH R01 AG049483 grant; the Glenn Foundation for Medical Research Glenn Award for Research in Biological Mechanisms of Aging; a New Scholar in Aging Award from the Lawrence Ellison Foundation; the Baxter Family Foundation; and to Malene Hansen, an NIH R01 GM117466 grant. A new form of symbiosis that is based on respiration and transfer of energy is to this date unprecedented. Energy-providing bacterial endosymbiont enables its unicellular eukaryotic host to breathe nitrate, demonstrating that unicellular eukaryotes may acquire endosymbionts to complement or replace functions of their mitochondrial organelles. Researchers from Bremen, together with their colleagues from the Max Planck Genome Center in Cologne and the aquatic research institute Eawag from Switzerland, have discovered a unique bacterium that lives inside a unicellular eukaryote and provides it with energy. Unlike mitochondria, this so-called endosymbiont derives energy from the respiration of nitrate, not oxygen. “Such partnership is completely new,” says Jana Milucka, the senior author on the Nature paper. “A symbiosis that is based on respiration and transfer of energy is to this date unprecedented.” In general, among eukaryotes, symbioses are rather common. Eukaryotic hosts often co-exist with other organisms, such as bacteria. Some of the bacteria live inside the host cells or tissue, and perform certain services, such as defense or nutrition. In return, the host provides shelter and suitable living conditions for the symbiont. An endosymbiosis can even go that far that the bacterium loses its ability to survive on its own outside its host. This was also the case with the symbiosis discovered by the Bremen scientists in Lake Zug in Switzerland. “Our finding opens the possibility that simple unicellular eukaryotes, such as protists, can host energy-providing endosymbionts to complement or even replace the functions of their mitochondria,” says Jon Graf, first author of the study. “This protist has managed to survive without oxygen by teaming up with an endosymbiont capable of nitrate respiration.” The endosymbiont’s name ‘Candidatus Azoamicus ciliaticola’ reflects this; a ‘nitrogen friend’ that dwells within a ciliate. The figure is a composite of a scanning electron microscope image (SEM, grey) and fluorescence images. Visible is the ‘Candidatus Azoamicus ciliaticola’ endosymbiont (visualized by FISH, yellow) and bacterial prey in food vacuoles as well as the large cell nucleus (stained by DAPI, blue). The outer structure of the weakly fluorescent ciliate as well as the cilia are also visible. Credit: Max Planck Institute for Marine Microbiology, S. Ahmerkamp An Intimate Partnership Becomes Ever Closer So far, it has been assumed that eukaryotes in oxygen-free environments survive through fermentation, since mitochondria require oxygen in order to generate energy. The fermentation process is well documented and has been observed in many anaerobic ciliates. However, microorganisms cannot draw as much energy from fermentation, and they typically do not grow and divide as quickly as their aerobic counterparts. “Our ciliate has found a solution for this,” says Graf. “It has engulfed a bacterium with the ability to breathe nitrate and integrated it into its cell. We estimate that the assimilation took place at least 200 to 300 million years ago.” Since then, evolution has further deepened this intimate partnership. Time-Shifted Evolution The evolution of mitochondria has proceeded in a similar way. „All mitochondria have a common origin,” explains Jana Milucka. It is believed that more than a billion years ago when an ancestral archaeon engulfed a bacterium, these two started a very important symbiosis: this event marked the origin of the eukaryotic cell. Over time, the bacterium became more and more integrated into the cell, progressively reducing its genome. Properties no longer needed were lost and only the ones that benefited the host were retained. Eventually, mitochondria evolved, as we know them today. They have their own tiny genome as well as a cell membrane, and exist as so-called organelles in eukaryotes. In the human body, for example, they are present in almost every cell and supply them – and thus us – with energy. “Our endosymbiont is capable of performing many mitochondrial functions, even though it does not share a common evolutionary origin with mitochondria,” says Milucka. “It is tempting to speculate that the symbiont might follow the same path as mitochondria, and eventually become an organelle.” A Chance Encounter It is actually amazing that this symbiosis has remained unknown for so long. Mitochondria work so well with oxygen – why shouldn’t there be an equivalent for nitrate? One possible answer is that no one was aware of this possibility and so no one was looking for it. Studying endosymbioses is challenging, as most symbiotic microorganisms cannot be grown in the laboratory. However, the recent advances in metagenomic analyses have allowed us to gain a better insight into the complex interaction between hosts and symbionts. When analyzing a metagenome, scientists look at all genes in a sample. This approach is often used for environmental samples as the genes in a sample cannot be automatically assigned to the organisms present. This means that scientists usually look for specific gene sequences that are relevant to their research question. Metagenomes often contain millions of different gene sequences and it is quite normal that only a small fraction of them is analyzed in detail. Originally, the Bremen scientists were also looking for something else. The Research Group Greenhouse Gases at the Max-Planck-Institute for Marine Microbiology investigates microorganisms involved in methane metabolism. For this, they have been studying the deep-water layers of Lake Zug. The lake is highly stratified, which means that there is no vertical exchange of water. The deep-water layers of Lake Zug thus have no contact with surface water and are largely isolated. That is why they contain no oxygen but are rich in methane and nitrogen compounds, such as nitrate. While looking for methane-munching bacteria with genes for nitrogen conversion, Graf came across an amazingly small gene sequence that encoded the complete metabolic pathway for nitrate respiration. “We were all stunned by this finding and I started comparing the DNA with similar gene sequences in a database,” says Graf. But the only similar DNA belonged to that of symbionts that live in aphids and other insects. “This didn’t make sense. How would insects get into these deep waters? And why?,” Graf remembers. The scientists of the research group started guessing games and betting. Not Alone in the Dark Lake In the end, one thought prevailed: The genome must belong to a yet-unknown endosymbiont. To verify this theory, members of the research team undertook several expeditions to Lake Zug in Switzerland. With the help of the local cooperation partner Eawag they collected samples to look specifically for the organism that contains this unique endosymbiont. In the lab, the scientists fished out various eukaryotes out of the water samples with a pipette. At last, using a gene marker, it was possible to visualize the endosymbiont and identify its protist host. A final excursion one year ago was supposed to bring final certainty. It was a difficult undertaking in the middle of winter. Stormy weather, dense fog and time pressure due to the first news about Coronavirus as well as a possible lockdown made the search in the big lake even more difficult. Nonetheless, the scientists succeeded in retrieving several samples from the deep water and bringing them to Bremen. These samples brought them final confirmation of their theory. “It is nice knowing that they are down there together,” says Jana Milucka. “Normally, these ciliates eat bacteria. But this one let one alive and partnered up with it.” Many New Questions This finding provokes many exciting new questions. Are there similar symbioses that have existed much longer and where the endosymbiont has already crossed the boundary to an organelle? If such symbiosis exists for nitrate respiration, does it also exist for other compounds? How did this symbiosis, which has existed for 200 to 300 million years, end up in a post-glacial lake in the Alps that only formed 10,000 years ago? Moreover: “Now that we know what we are looking for, we found the endosymbiont’s gene sequences all around the world,” says Milucka. In France, as well as in Taiwan, or in East African lakes that in part are much older than Lake Zug. Does the origin of this symbiosis lie in one of them? Or did it start in the ocean? These are the questions that the research group wants to investigate next. Reference: “Anaerobic endosymbiont generates energy for ciliate host by denitrification” by Jon S. Graf, Sina Schorn, Katharina Kitzinger, Soeren Ahmerkamp, Christian Woehle, Bruno Huettel, Carsten J. Schubert, Marcel M. M. Kuypers and Jana Milucka, 3 March 2021, Nature. DOI: 10.1038/s41586-021-03297-6 Eukaryotic Toeholds (eToeholds) are engineered RNA-based control elements that, as in this example, can be specifically activated by viral “trigger RNAs” to enable synthesis of a reporter protein and thus signal the presence of the virus. I the future, eToeholds could be used to design safer and more specific RNA therapeutics, RNA diagnostics, and strategies to enrich therapeutic cell types in in vitro differentiation approaches. Credit: Wyss Institute at Harvard University eToeholds are engineered control elements that could make RNA therapeutics safer, cell therapies more effective, and enable novel forms of biodetection. RNAs are best known as the molecules that translate information encoded in genes into proteins with their myriad of activities. However, because of their structural complexity and relative stability, RNA also has attracted great attention as a valuable biomaterial that can be used to create new types of therapies, synthetic biomarkers, and, of course, potent vaccines as we have learned from the COVID-19 pandemic. Delivering a synthetic RNA molecule into a cell essentially instructs it to produce a desired protein, which can then carry out therapeutic, diagnostic, and other functions. A key challenge for researchers has been to only allow cells causing or affected by a specific disease to express the protein and not others. This ability could significantly streamline production of the protein in the body and avoid unwanted side effects. Now, a team of synthetic biologists and cell engineers led by James J. Collins, Ph.D. at the Wyss Institute for Biologically Inspired Engineering and Massachusetts Institute of Technology (MIT), has developed eToeholds – small versatile devices built into RNA that enable expression of a linked protein-encoding sequence only when a cell-specific or viral RNA is present. eToehold devices open up multiple opportunities for more targeted types of RNA therapy, in vitro cell and tissue engineering approaches, and the sensing of diverse biological threats in humans and other higher organisms. The findings are reported in Nature Biotechnology. In 2014, Collins’ team, together with that of Wyss Core Faculty member Peng Yin, Ph.D., successfully developed toehold switches for bacteria that are expressed in an off-state and respond to specific trigger RNAs by turning on the synthesis of a desired protein by the bacterial protein synthesizing machinery. However, the bacterial toehold design cannot be used in more complex cells, including human cells, with their more complicated architecture and protein synthesizing apparatus. “In this study, we took IRES [internal ribosome entry sites] elements, a type of control element common in certain viruses, which harness the eukaryotic protein translating machinery, and engineered them from the ground up into versatile devices that can be programed to sense cell or pathogen-specific trigger RNAs in human, yeast, and plant cells,” said Collins. “eToeholds could enable more specific and safer RNA therapeutic and diagnostic approaches not only in humans but also plants and other higher organisms, and be used as tools in basic research and synthetic biology.” The control elements known as “internal ribosome entry sites,” in short IRESs, are sequences found in viral RNA that allow the host cell’s protein-synthesizing ribosomes access to a segment of the viral genome next to a sequence encoding a viral protein. Once latched on to the RNA, ribosomes start scanning the protein encoding sequence, while simultaneously synthesizing the protein by sequentially adding corresponding amino acids to its growing end. “We forward-engineered IRES sequences by introducing complementary sequences that bind to each other to form inhibitory base-paired structures, which prevent the ribosome from binding the IRES,” said co-first author Evan Zhao, Ph.D., who is a Postdoctoral Fellow on Collins’ team. “The hairpin loop-encoding sequence element in eToeholds is designed such that it overlaps with specific sensor sequences that are complementary to known trigger RNAs. When the trigger RNA is present and binds to its complement in eToeholds, the hairpin loop breaks open and the ribosome can switch on to do its job and produce the protein.” Zhao teamed up with co-first author and Wyss Technology Development Fellow Angelo Mao, Ph.D., in the eToehold project, which enabled them to combine their respective areas of expertise in synthetic biology and cell engineering to break new ground in the manipulation of IRES sequences. In a process of quick iteration, they were able to design and optimize eToeholds that were functional in human and yeast cells, as well as cell-free protein-synthesizing assays. They achieved up to 16-fold induction of fluorescent reporter genes linked to eToeholds exclusively in the presence of their appropriate trigger RNAs, compared to control RNAs. “We engineered eToeholds that specifically detected Zika virus infection and the presence of SARS-CoV-2 viral RNA in human cells, and other eToeholds triggered by cell-specific RNAs like, for example, an RNA that is only expressed in skin melanocytes,” said Mao. “Importantly, eToeholds and the sequences encoding desired proteins linked to them can be encoded in more stable DNA molecules, which when introduced into cells are converted into RNA molecules that are tailored to the type of protein expression we intended. This expands the possibilities of eToehold delivery to target cells.” The researchers believe that their eToehold platform could help target RNA therapies and some gene therapies to specific cell types, which is important as many such therapies are hampered by excessive off-target toxicities. In addition, it could facilitate ex vivo differentiation approaches that guide stem cells along developmental pathways to generate specific cell types for cell therapies and other applications. The conversion of stem cells and intermediate cells along many differentiating cell lineages often is not very effective, and eToeholds could help with enriching desired cell types. “This study highlights how Jim Collins and his team on the Wyss Living Cellular Device platform are developing innovative tools that can advance the development of more specific, safe, and effective RNA and cellular therapies, and so positively impact on the lives of many patients,” said Wyss Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences. For more on this study, see RNA Control Switch: Engineers Devise a Way To Selectively Turn On Gene Therapies in Human Cells. Reference: “RNA-responsive elements for eukaryotic translational control” by Evan M. Zhao, Angelo S. Mao, Helena de Puig, Kehan Zhang, Nathaniel D. Tippens, Xiao Tan, F. Ann Ran, Isaac Han, Peter Q. Nguyen, Emma J. Chory, Tiffany Y. Hua, Pradeep Ramesh, David B. Thompson, Crystal Yuri Oh, Eric S. Zigon, Max A. English and James J. Collins, 28 October 2021, Nature Biotechnology. DOI: 10.1038/s41587-021-01068-2 Other authors on the study are Helena de Puig, Ph.D., Kehan Zhang, Ph.D., Nathaniel Tippens, Ph.D., Xiao Tan, M.D., F. Ann Ran, Ph.D., Wyss Research Assistant Isaac Han, Peter Nguyen, Ph.D., Emma Chory, Ph.D., Tiffany Hua, Pradeep Ramesh, Ph.D., Wyss Staff Scientist David Thompson, Ph.D., Crystal Yuri Oh, Eric Zigon, and Max English. The study was funded by grants from BASF, the NIH (under grant #RC2 DK120535-01A1), and the Wyss Institute for Biologically Inspired Engineering. RRG455KLJIEVEWWF |
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