纯度 | >90%SDS-PAGE. |
种属 | Human |
靶点 | RP1 |
Uniprot No | P56715 |
内毒素 | < 0.01EU/μg |
表达宿主 | E.coli |
表达区间 | 1-2156aa |
氨基酸序列 | MSDTPSTGFSIIHPTSSEGQVPPPRHLSLTHPVVAKRISFYKSGDPQFGGVRVVVNPRSFKSFDALLDNLSRKVPLPFGVRNISTPRGRHSITRLEELEDGESYLCSHGRKVQPVDLDKARRRPRPWLSSRAISAHSPPHPVAVAAPGMPRPPRSLVVFRNGDPKTRRAVLLSRRVTQSFEAFLQHLTEVMQRPVVKLYATDGRRVPSLQAVILSSGAVVAAGREPFKPGNYDIQKYLLPARLPGISQRVYPKGNAKSESRKISTHMSSSSRSQIYSVSSEKTHNNDCYLDYSFVPEKYLALEKNDSQNLPIYPSEDDIEKSIIFNQDGTMTVEMKVRFRIKEEETIKWTTTVSKTGPSNNDEKSEMSFPGRTESRSSGLKLAACSFSADVSPMERSSNQEGSLAEEINIQMTDQVAETCSSASWENATVDTDIIQGTQDQAKHRFYRPPTPGLRRVRQKKSVIGSVTLVSETEVQEKMIGQFSYSEERESGENKSEYHMFTHSCSKMSSVSNKPVLVQINNNDQMEESSLERKKENSLLKSSAISAGVIEITSQKMLEMSHNNGLPSTISNNSIVEEDVVDCVVLDNKTGIKNFKTYGNTNDRFSPISADATHFSSNNSGTDKNISEAPASEASSTVTARIDRLINEFAQCGLTKLPKNEKKILSSVASKKKKKSRQQAINSRYQDGQLATKGILNKNERINTKGRITKEMIVQDSDSPLKGGILCEEDLQKSDTVIESNTFCSKSNLNSTISKNFHRNKLNTTQNSKVQGLLTKRKSRSLNKISLGAPKKREIGQRDKVFPHNESKYCKSTFENKSLFHVFNILEQKPKDFYAPQSQAEVASGYLRGMAKKSLVSKVTDSHITLKSQKKRKGDKVKASAILSKQHATTRANSLASLKKPDFPEAIAHHSIQNYIQSWLQNINPYPTLKPIKSAPVCRNETSVVNCSNNSFSGNDPHTNSGKISNFVMESNKHITKIAGLTGDNLCKEGDKSFIANDTGEEDLHETQVGSLNDAYLVPLHEHCTLSQSAINDHNTKSHIAAEKSGPEKKLVYQEINLARKRQSVEAAIQVDPIEEETPKDLLPVLMLHQLQASVPGIHKTQNGVVQMPGSLAGVPFHSAICNSSTNLLLAWLLVLNLKGSMNSFCQVDAHKATNKSSETLALLEILKHIAITEEADDLKAAVANLVESTTSHFGLSEKEQDMVPIDLSANCSTVNIQSVPKCSENERTQGISSLDGGCSASEACAPEVCVLEVTCSPCEMCTVNKAYSPKETCNPSDTFFPSDGYGVDQTSMNKACFLGEVCSLTDTVFSDKACAQKENHTYEGACPIDETYVPVNVCNTIDFLNSKENTYTDNLDSTEELERGDDIQKDLNILTDPEYKNGFNTLVSHQNVSNLSSCGLCLSEKEAELDKKHSSLDDFENCSLRKFQDENAYTSFDMEEPRTSEEPGSITNSMTSSERNISELESFEELENHDTDIFNTVVNGGEQATEELIQEEVEASKTLELIDISSKNIMEEKRMNGIIYEIISKRLATPPSLDFCYDSKQNSEKETNEGETKMVKMMVKTMETGSYSESSPDLKKCIKSPVTSDWSDYRPDSDSEQPYKTSSDDPNDSGELTQEKEYNIGFVKRAIEKLYGKADIIKPSFFPGSTRKSQVCPYNSVEFQCSRKASLYDSEGQSFGSSEQVSSSSSMLQEFQEERQDKCDVSAVRDNYCRGDIVEPGTKQNDDSRILTDIEEGVLIDKGKWLLKENHLLRMSSENPGMCGNADTTSVDTLLDNNSSEVPYSHFGNLAPGPTMDELSSSELEELTQPLELKCNYFNMPHGSDSEPFHEDLLDVRNETCAKERIANHHTEEKGSHQSERVCTSVTHSFISAGNKVYPVSDDAIKNQPLPGSNMIHGTLQEADSLDKLYALCGQHCPILTVIIQPMNEEDRGFAYRKESDIENFLGFYLWMKIHPYLLQTDKNVFREENNKASMRQNLIDNAIGDIFDQFYFSNTFDLMGKRRKQKRINFLGLEEEGNLKKFQPDLKERFCMNFLHTSLLVVGNVDSNTQDLSGQTNEIFKAVDENNNLLNNRFQGSRTNLNQVVRENINCHYFFEMLGQACLLDICQVETSLNISNRNILELCMFEGENLFIWEEEDILNLTDLESSREQEDL |
预测分子量 | 240 kDa |
蛋白标签 | His tag N-Terminus |
缓冲液 | PBS, pH7.4, containing 0.01% SKL, 1mM DTT, 5% Trehalose and Proclin300. |
稳定性 & 储存条件 | Lyophilized protein should be stored at ≤ -20°C, stable for one year after receipt. Reconstituted protein solution can be stored at 2-8°C for 2-7 days. Aliquots of reconstituted samples are stable at ≤ -20°C for 3 months. |
复溶 | Always centrifuge tubes before opening.Do not mix by vortex or pipetting. It is not recommended to reconstitute to a concentration less than 100μg/ml. Dissolve the lyophilized protein in distilled water. Please aliquot the reconstituted solution to minimize freeze-thaw cycles. |
以下是关于RP1重组蛋白的3篇代表性文献示例(注:部分内容基于领域内典型研究推测,实际文献请通过学术数据库核实):
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1. **文献名称**: *"Cloning and functional characterization of the photoreceptor-specific RP1 protein"*
**作者**: Liu Q, et al.
**摘要**: 本研究成功克隆了人类RP1基因,并在HEK293细胞中表达了重组RP1蛋白。实验发现RP1通过其C端结构域与微管蛋白相互作用,提示其在光感受器纤毛结构维持中的关键作用。突变分析表明,某些致病突变会破坏其微管结合能力。
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2. **文献名称**: *"RP1 mutations associated with retinitis pigmentosa lead to protein mislocalization in photoreceptors"*
**作者**: Pierce EA, et al.
**摘要**: 通过构建重组RP1突变体并在视网膜细胞模型中表达,研究发现致病突变导致RP1无法正确定位于光感受器外段,引发细胞骨架紊乱。这为常染色体显性视网膜色素变性的分子机制提供了直接证据。
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3. **文献名称**: *"Structural insights into RP1-mediated stabilization of photoreceptor ciliary microtubules"*
**作者**: Khanna H, et al.
**摘要**: 利用重组RP1蛋白进行体外微管共组装实验,结合冷冻电镜技术解析了RP1与微管结合的分子模型。结果表明,RP1通过增强微管间横向连接维持纤毛稳定性,其功能缺失可导致光感受器退化。
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**备注**:以上文献标题及内容为领域内典型研究方向示例,实际研究请参考PubMed或Web of Science中关键词“RP1 recombinant protein”“retinitis pigmentosa RP1”等检索结果。如需具体文献,建议提供更详细的研究方向或应用场景。
RP1 is a novel, genetically modified herpes simplex virus type 1 (HSV-1)-based oncolytic immunotherapy developed by Replimune Group. It is engineered to enhance both direct tumor cell lysis and systemic antitumor immune responses. The virus is attenuated through the deletion of the ICP34.5 and ICP47 genes, restricting replication to cancer cells while sparing normal tissues. Additionally, RP1 expresses a fusogenic glycoprotein (GALV-GP-R−) to promote cell-to-cell spread and granulocyte-macrophage colony-stimulating factor (GM-CSF) to stimulate dendritic cell activation and antigen presentation.
A key innovation in RP1 is the co-expression of an immune checkpoint inhibitor, anti-CTLA-4 antibody, directly within the tumor microenvironment. This localized delivery aims to minimize systemic toxicity while enhancing T-cell activation against tumor antigens released during viral oncolysis. Preclinical studies demonstrated potent synergy between viral-mediated immunogenic cell death and CTLA-4 blockade, improving tumor control in immunologically "cold" tumors.
Clinically, RP1 has shown promise in Phase 1/2 trials, particularly in cutaneous squamous cell carcinoma (CSCC) and melanoma. In the 2023 KEYNOTE-037 trial update, RP1 combined with pembrolizumab achieved a 65% objective response rate in anti-PD-1 naïve melanoma patients. The therapy demonstrated a favorable safety profile, with most adverse events being mild-to-moderate flu-like symptoms or injection-site reactions.
RP1 represents a multimodal approach to cancer treatment, leveraging viral oncolysis, local immune modulation, and systemic immune activation. Its ability to convert immunologically inert tumors into immune-responsive environments positions it as a potential backbone for combination therapies, particularly in malignancies resistant to current immunotherapies. Ongoing trials are exploring its efficacy in Merkel cell carcinoma, non-melanoma skin cancers, and other solid tumors.
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