核酸新藥設計、動物模式驗證、 藥品開發與轉譯——三項核心能力Three Core Capabilities: Nucleic Acid Drug Design, Animal Model Validation, and Drug Development & Translation
台基核建立自主的 ASO 核酸新藥設計與篩選平台，並以自建動物模式驗證候選藥物效力；同時透過新劑型開發專案，累積從配方測試到法規申請的完整執行經驗。三項能力各自獨立發展，共同支撐公司的核酸新藥開發與產品化目標。CoGentide has built a proprietary ASO design and screening platform, and validates candidate drug efficacy through our own animal models. In parallel, our new formulation development programs demonstrate our execution capability. All three capabilities are developed independently, together supporting our nucleic acid drug development and commercialization goals.
ASO 核酸新藥設計與篩選平台ASO Novel Drug Design and Screening Platform
反義寡核苷酸（ASO）透過與目標 mRNA 精準配對，調節致病基因之表現。我們建立 Dry Lab／Wet Lab 雙軌篩選流程：Dry Lab 階段自主設計序列篩選邏輯與評估標準，演算參數涵蓋序列二級結構、結合能量（binding energy）與脫靶機率等面向，並建立自動化篩選流程；Wet Lab 階段則建構細胞篩選平台，進一步驗證候選序列之基因表現抑制能力與安全性。Antisense oligonucleotides (ASOs) modulate disease-gene expression by binding precisely to target mRNA. We've built a dual Dry Lab / Wet Lab screening workflow: in the Dry Lab stage, we independently design sequence screening logic and evaluation criteria — with algorithmic parameters including secondary structure, binding energy, and off-target probability. In the Wet Lab stage, we maintain a cell-based screening platform to further validate candidate sequences for gene-suppression activity and safety.
為驗證平台之篩選能力，我們以三款已上市 ASO 藥物之標靶序列作為對照組進行測試：以 Qalsody（tofersen）之 SOD1 標靶序列為對照，篩選之候選序列於 HepG2 細胞株中，抑制效果優於陽性對照組（相對表現量 0.47 vs. 0.67，p<0.05）；以 Tegsedi（inotersen）之 TTR 標靶序列為對照，篩選之候選序列於 HepG2 細胞株中，抑制效果優於陽性對照組（相對表現量 0.45 vs. 0.74），並達統計顯著（p<0.01）；以 Waylivra（volanesorsen）之 APOC3 標靶序列為對照，篩選之候選序列於 PLC5 細胞株中，基因表現抑制程度與陽性對照組相當。上述結果顯示，本平台篩選之候選序列，其基因表現抑制能力可達到、甚至優於已上市藥物之標靶序列表現。To validate our platform's screening capability, we benchmarked candidate sequences against the target sequences of three marketed ASO drugs. Against Qalsody's (tofersen) SOD1 target sequence, our candidate sequence outperformed the positive control in HepG2 cells (relative expression 0.47 vs. 0.67, p<0.05). Against Tegsedi's (inotersen) TTR target sequence, our candidate sequence outperformed the positive control in HepG2 cells (relative expression 0.45 vs. 0.74), reaching statistical significance (p<0.01). Against Waylivra's (volanesorsen) APOC3 target sequence, our candidate sequence showed gene-suppression comparable to the positive control in PLC5 cells. These results demonstrate that our platform's screened candidate sequences achieve gene-suppression performance comparable to, or exceeding, that of the target sequences of marketed drugs.
以此平台為基礎，我們已針對端粒酶（TERT）完成候選序列篩選與細胞功效驗證，並確認候選藥物，現正推進臨床前測試。Building on this platform, we have completed candidate sequence screening and cell-based efficacy validation for TERT (telomerase), identified a lead candidate, and are now advancing it into preclinical testing.
qPCR ／ ELISA 雙重驗證qPCR / ELISA Dual Validation
以 qPCR 檢測 APOC3 mRNA 相對表現量（上圖，誤差線為標準差），並以 ELISA 檢測 HepG2 細胞株培養液中分泌之 APOC3 蛋白濃度（下圖），進行雙重驗證。兩項獨立試驗結果一致顯示，候選序列 hAPOC3-05 與 hAPOC3-07 之抑制效果最為顯著。PC：陽性對照組；NC：陰性對照組。APOC3 mRNA relative expression was measured by qPCR (top; error bars represent SD), and secreted APOC3 protein concentration was measured by ELISA in HepG2 cell culture medium (bottom). Both independent assays consistently identify hAPOC3-05 and hAPOC3-07 as the most potent suppressors. PC: positive control; NC: negative control.
免疫健全肝腫瘤動物模式Immunocompetent Liver Tumor Animal Model
為驗證候選序列在疾病情境下之實際效果，我們建立免疫健全 HBV 相關肝腫瘤動物模式：透過特定基因組合精準嵌合至免疫功能正常小鼠之肝細胞基因體中，同時導入免疫選擇壓力，模擬病患於發炎性肝臟微環境中腫瘤發生與免疫清除之動態過程。相較於傳統免疫缺陷小鼠模型，本模式具備完整免疫微環境與高成瘤重現性，並整合非侵入式活體追蹤指標，可作為候選新藥藥效驗證之關鍵平台。本模式亦可延伸應用於其他肝臟腫瘤候選藥物之篩選驗證。To validate candidate sequences in a disease-relevant setting, we've developed an immunocompetent HBV-related liver tumor model: specific gene combinations are precisely integrated into the hepatocyte genome of immunocompetent mice, together with induced immune selection pressure, to simulate tumor development and immune clearance within an inflammatory liver microenvironment. Compared to conventional immunodeficient mouse models, our model offers an intact immune microenvironment, high tumor reproducibility, and integrated non-invasive in vivo tracking.
專利狀態：PCT 專利申請號 PCT/CN2025/090113（已申請，尚未公開）；台灣專利申請號 114115045（已申請，尚未公開）。智慧財產權歸屬台基核。Patent Status: PCT application PCT/CN2025/090113 (filed, not yet published); Taiwan application 114115045 (filed, not yet published). IP rights held by CoGentide.
IVIS 活體螢光造影IVIS In Vivo Imaging
同一動物模式於不同時間點之腫瘤生成與訊號強度變化。Tumor development and signal intensity tracked over time in the same animal model.
藥品開發執行與轉譯能力Drug Development Execution and Translational Capability
我們透過505(b)(2) 法規路徑，推進既有上市藥物之新劑型開發專案。此能力獨立於核酸新藥開發之外，由台基核團隊主導配方測試、臨床前開發與法規申請作業，驗證團隊將候選標的推進至臨床申請之完整執行力，同時為公司建立穩健之產品化與營收基礎。We pursue new formulation development for marketed drugs through the 505(b)(2) regulatory pathway. This capability is developed independently from our nucleic acid drug programs, with CoGentide's team leading formulation testing, preclinical development, and regulatory filing — demonstrating our full execution capability while building a stable foundation for commercialization and revenue.
深入了解我們的研發項目Explore Our R&D Programs
查看台基核目前推進中的核酸新藥與新劑型開發專案進度。See the current progress of CoGentide's nucleic acid drug and formulation development programs.
