Development and applications of high-efficiency gene targeting in human cells

• Project/Area Number: 24310149
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Applied genomics
• Research Institution: Yokohama City University
• Principal Investigator: ADACHI NORITAKA 横浜市立大学, 生命ナノシステム科学研究科(八景キャンパス), 教授 (30264675)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000); Fiscal Year 2014: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2013: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000); Fiscal Year 2012: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: ゲノム改変 / ジーンターゲティング / ランダム挿入

Outline of Final Research Achievements

We have been developing systems that enable rapid production of human cell lines with the use of plasmid-based DNA vectors. In this research project, we have conducted basic studies aimed at developing ultrahigh-efficiency gene-targeting systems, particularly in terms of controlling random integration, a mechanism that acts to reduce the efficiency of gene targeting.

Research Products

• [Journal Article] Role for Artemis nuclease in the repair of radiation-induced DNA double strand breaks by alternative end joining. (2015)
  • Author(s): Moscariello M, Wieloch R, Kurosawa A, Li F, Adachi N, Mladenov E, Iliakis G.
  • Journal Title: DNA Repair Volume: 31 Pages: 29-40
  • DOI: 10.1016/j.dnarep.2015.04.004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of Auf1 in elimination of oxidatively damaged messenger RNA in human cells. (2015)
  • Author(s): Ishii T, Hayakawa H, Sekiguchi T, Adachi N, Sekiguchi M.
  • Journal Title: Free Radic Biol Med. Volume: 79 Pages: 109-116
  • DOI: 10.1016/j.freeradbiomed.2014.11.018
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Analysis of the role of homology arms in gene-targeting vectors in human cells. (2014)
  • Author(s): Ishii A, Kurosawa A, Saito S, Adachi N.
  • Journal Title: PLoS One Volume: 9 Issue: 9 Pages: e108236-e108236
  • DOI: 10.1371/journal.pone.0108236
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] DNA Ligase IV and Artemis Act Cooperatively to Suppress Homologous Recombination in Human Cells: Implications for DNA Double-Strand Break Repair. (2013)
  • Author(s): Kurosawa A, Saito S, So S, Hashimoto M, Iwabuchi K, Watabe H, Adachi N.
  • Journal Title: PLoS One Volume: 8 Issue: 8 Pages: e72253-e72253
  • DOI: 10.1371/journal.pone.0072253
  • Peer Reviewed
• [Journal Article] Endogenous factors causative of spontaneous DNA damage that leads to random integration in human cells. (2013)
  • Author(s): N. Adachi et al.
  • Journal Title: Gene Technology Volume: 2 Issue: 01 Pages: 105-105
  • DOI: 10.4172/2329-6682.1000105
  • Peer Reviewed
• [Journal Article] Both CpG methylation and AID are required for the fragility of the human Bcl-2 major breakpoint region: Implications for the timing of the breaks in the t(14;18) (2013)
  • Author(s): N. Adachi, et al.
  • Journal Title: Mol. Cell. Biol Volume: 33 Pages: 947-957
  • Peer Reviewed
• [Journal Article] Artemis C-terminal region facilitates efficient V(D)J recombination through its interaction with both DNA Ligase IV and DNA-PKcs. (2012)
  • Author(s): N. Adachi, et al.
  • Journal Title: J.Exp. Med. Volume: 209 Issue: 5 Pages: 955-963
  • DOI: 10.1084/jem.20111437
  • Peer Reviewed
• [Patent(Industrial Property Rights)] 遺伝子ターゲティングベクター及びその利用方法 (2012)
  • Inventor(s): 足立典隆
  • Industrial Property Rights Holder: 足立典隆
  • Filing Date: 2012-12-12
  • Overseas
• [Patent(Industrial Property Rights)] 遺伝子ターゲティングベクター, その作製方法及び利用方法 (2012)
  • Inventor(s): 足立典隆
  • Industrial Property Rights Holder: 足立典隆
  • Filing Date: 2012-05-24
  • Overseas