Raw materials for GMP mRNA manufacturing | Thermo Fisher Scientific

通过精选优质原材料，加速mRNA疗法研发与商业化进程。赛默飞世尔科技（Thermo Fisher Scientific）为您提供覆盖mRNA疗法全开发周期的广泛产品与服务，包括研究与发现、临床前开发、临床开发及商业化生产。

Figure 1. mRNA manufacturing workflow

RNA药物开发的质量等级标准

标准级（Standard Grade）——支持RNA发现与研究，适用于基础RNA研究，提供广泛的材料选择。采用高质量试剂，配方和生产工艺中可能含动物源成分（AO）。提供标准质量文件包支持。
TheraPure级——助力早期开发与工艺优化，适用于RNA药物生产工艺开发、优化及临床前研究初期阶段。无动物源成分（AOF）且不含β-内酰胺类物质。与TheraPure GMP级采用相同分子和配方，便于后续向GMP级别平稳过渡。
TheraPure GMP级——满足临床与商业化生产需求，适用于mRNA生产进入临床试验及商业化cGMP阶段。严格的生产工艺与质量控制标准。提供完整的监管申报支持文件包。（观看质量介绍视频了解更多）

不同质量等级的产品属性、生产工艺及可提供的质控文件包方面均存在差异。具体主要差异请参见表1。

Product	Standard	TheraPure	TheraPure GMP
AOF (animal origin free) and beta-lactam free process and materials	No	Yes	Yes
AOF and beta-lactam free facility	No	No	Yes
Manufacture and documentation follow ICH Q7 guidelines	No	No	Yes
Validated product-specific manufacturing processes and analytical methods	No	No	Yes
Product-specific stability	No	No	Yes
Impurity testing, including melamine and nitrosamine	No	No	Yes
Quality documentation	CoA, CoO	CoA, CoO, TSE/BSE statement	CoA, CoO, TSE/BSE statement, impurity profiles
DMF (drug master file)	No	No	Yes
Recommended use	Research use only	Proof of concept, research, and pre-clinical development	Clinical and commercial manufacturing

mRNA的生产流程包括DNA模板制备、体外转录（IVT）、mRNA修饰以及DNA与蛋白去除等关键步骤。我们提供创新的解决方案与定制化服务，精准满足您对产品质量、纯度要求以及可扩展的批次间一致性的需求。

DNA template preparation in vitro

Plasmid DNA linearization

mRNA transcription

mRNA modification

DNA template and protein removal

体外DNA模板可通过滚环扩增（RCA）或PCR等技术制备。作为一种无细胞扩增技术，RCA是传统质粒DNA和PCR扩增的理想替代方案。该技术需使用具有强链置换活性的DNA聚合酶及dNTPs进行链合成，整个反应在恒温条件下完成。

Product	Standard	TheraPure	TheraPure GMP
Phi29 DNA polymerase	EP0091	TheraPure phi29 DNA Polymerase (10 U/μL)	-
dNTPs	dNTP Set, 100 mM Solutions	-	TheraPure GMP dNTPs

采用限制性内切酶对质粒DNA进行线性化处理，所得线性化DNA将作为体外转录（IVT）的模板用于mRNA制备。

Product	Standard	TheraPure	TheraPure GMP
Eam1104I restriction enzyme	Eam1104I (EarI) (10 U/μL)	TheraPure restriction enzymes	TheraPure GMP Eam1104I Restriction Enzyme, 20 U/μL

在体外转录（IVT）反应过程中，DNA模板、RNA聚合酶、核苷三磷酸（NTPs）、RNase抑制剂、焦磷酸酶以及IVT反应缓冲体系是mRNA合成的关键要素。

Product	Standard	TheraPure	TheraPure GMP
T7 RNA polymerase	T7 RNA Polymerase, HC (200 U/μL)	TheraPure RNA polymerases	TheraPure GMP T7 RNA Polymerase, 200 U/μL
SP6 RNA polymerase	SP6 RNA Polymerase, HC (≥100 U/μL)	-	-
Ribonuclease inhibitor	RiboLock RNase Inhibitor (40 U/μL)	TheraPure modifying enzymes	TheraPure GMP RNase Inhibitor, 40 U/μL
Pyrophosphatase, inorganic	Pyrophosphatase, inorganic (0.1 U/μL)	TheraPure modifying enzymes	TheraPure GMP Pyrophosphatase, inorganic, 0.1 U/μL
NTPs	NTP Set, Tris buffered NTP Set, 100 mM Solution	TheraPure nucleotides	TheraPure GMP nucleotides
N1-Methylpseudo-UTP	Contact us	-	TheraPure GMP N1-Methylpseudo-UTP, 100 mM sodium solution
IVT buffer	Buffers for RNA transcription and post-transcriptional modifications	-	Contact us

通过共转录修饰或转录后加帽处理，可有效保护mRNA分子并增强其功能活性。此外，poly-A尾的添加能够显著提升mRNA稳定性，防止其降解。

Product	Standard	TheraPure	TheraPure GMP
Vaccinia Capping Enzyme	Modifying enzymes	TheraPure Vaccinia Capping Enzyme, 100 U/µL	-
Vaccinia mRNA Cap 2'-O-Methyltransferase	Modifying enzymes	TheraPure 2'-O-Methyltransferase (125 U/μL)	-
S-Adenosyl-L-Methionine (SAM)	Co-factors	TheraPure S-Adenosyl-L-Methionine (32 mM)	Coming soon: TheraPure GMP S-Adenosyl-L-methionine, 32 mM
Poly A polymerase	Poly(A) Polymerase (cloned) 2 U/μL	-	-

IVT（体外转录）反应后，可通过DNA酶（如DNase）降解去除DNA模板；若需去除蛋白质成分，则可使用蛋白酶K（Proteinase K）进行处理。

Product	Standard	TheraPure	TheraPure GMP
DNAse I	DNase I, RNase-free, HC (50 U/μL)	TheraPure modifying enzymes	TheraPure GMP DNase I, RNase-free, 50 U/μL
Turbo DNAse	TURBO DNase (2 U/μL)	-	-
Proteinase K	Proteinase K, recombinant, PCR grade	-	-