Whole genome analysis and construction of a karyotype image analysis system for novel biopharmaceutical production host cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K04788
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 27040:Biofunction and bioprocess engineering-related
• Research Institution: Osaka University
• Principal Investigator: Yamano Noriko 大阪大学, 大学院工学研究科, 准教授 (20582795)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: バイオ医薬品 / 新規宿主細胞 / ゲノム

Outline of Final Research Achievements

Using DAPI images of chromosomes and multi-color FISH images, which can be displayed in different pseudocolors for each chromosome number, we constructed a karyotype image analysis system by creating a program to extract chromosome outline and color information using the Python language. I then analyzed karyotypes with chromosomal aberrations and their usefulness as host cells for recombinant protein production. I also showed that subclones with stable chromosomes can be obtained with a certain frequency even from parental strains with chromosomal instability, and that the acquired cells with stable chromosomes inherit their properties in subsequent generations. Futhermore, the comparison of the genomes of conventional CHO cells and CHL-YN cells provided information on the differences in genome structure and DNA methylation patterns.

Free Research Field

生物化学工学

Academic Significance and Societal Importance of the Research Achievements

CHO細胞は、バイオ医薬品の生産宿主細胞として産業利用されており、バイオ医薬品の多くがCHO細胞を用いて製造されている。従来のCHO細胞と比較して、倍速で増加するChinese hamster lung (CHL)-YN細胞をチャイニーズハムスターの肺組織から新たに樹立しており、これまでCHO細胞で行ってきた染色体不安定性に着目した細胞育種に加え、チャイニーズハムスター由来細胞の核型画像解析システムの構築と核型解析、また、CHO細胞、及び、CHL-YN細胞の全ゲノムシーケンスによるゲノム配列とDNAメチル化情報の取得を行った。これらは取得した新規宿主細胞の基盤情報及び基盤技術となる。