Genome editing and phenotyping of FAM46C using the CRISPR/Cas9 system

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16256
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Aichi Medical University
• Principal Investigator: KANASUGI Jo 愛知医科大学, 医学部, 助教 (00805450)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 多発性骨髄腫 / FAM46C遺伝子 / CRISPR/Cas9システム / ゲノム編集 / シグナル伝達経路 / 造腫瘍性 / 薬剤感受性

Outline of Final Research Achievements

Subcutaneous transplantation into mice was performed, and proliferation changes due to differences in FAM46C expression were observed. In the future, I will work on myeloma cell sorting and genome, RNA, and protein extraction using a magnetic activated cell sorting (MACS) device, which is necessary for sorting CD138-positive plasma cells from myeloma patient specimens. We planned to conduct research on the assumption that it would be applied to actual clinical practice. However, with the increase in medical care work associated with the epidemic of the new coronavirus infection, there were many unexpected tasks. Therefore, it became difficult to carry out research systematically, and it was not possible to secure sufficient research time. For the above reasons, we were unable to obtain research results.

Free Research Field

血液内科

Academic Significance and Societal Importance of the Research Achievements

骨髄染色体解析から、二倍体や転座、欠失・増幅の染色体異常は把握できるものの、骨髄腫の増悪に係わるゲノム異常や分子機構はよくわかっていない。近年、新規薬剤が一定の治療成績の向上を達成しているが、依然として治癒に至る例は少ない。初回の治療が奏功したように見えても短期間で再発する症例が多く、既存の薬剤では根治が極めて難しい。その最大の原因は、骨髄腫の悪性化と薬剤耐性であり、難治性骨髄腫を克服できる治療が切望されている。今回は十分な成果を得ることが困難であったが、本研究は、骨髄腫細胞の悪性化と進展に関わる病態の解明に活路を開き、実臨床での抗骨髄腫薬開発のブレイクスルーになると今後期待される。