Open Access

TALENs-mediated homozygous CCR5Δ32 mutations endow CD4+ U87 cells with resistance against HIV‑1 infection

  • Authors:
    • Ai Qing Yu
    • Yan Ding
    • Zhi Yong Lu
    • Yan Zhe Hao
    • Zhi Ping Teng
    • Shi Rong Yan
    • Dong Sheng Li
    • Yi Zeng
  • View Affiliations

  • Published online on: October 26, 2017     https://doi.org/10.3892/mmr.2017.7889
  • Pages:243-249
  • Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Since evidence suggests that transplantation of bone marrow stem cells with the C‑C chemokine receptor type 5 (CCR5)Δ32/Δ32 genotype may cure patients infected with human immunodeficiency virus (HIV)‑1, the present study aimed to reproduce the CCR5Δ32 mutation in cluster of differentiation (CD)4+ U87 cells using genome engineering methods. A modified transcription activator‑like effector nucleases (TALENs) technique, combined with homologous recombination for site‑specific, size‑controlled and homozygous DNA deletions, was used to reproduce the homozygous CCR5Δ32 mutation in CD4+ U87 cells. The results indicated that the frequency of the TALENs‑targeted mutation reached 50.4% without any selection, whereas homologous recombination from CCR5 to CCR5Δ32 occurred in 8.8% of targeted cells. Notably, a HIV‑1 challenge test demonstrated that CCR5Δ32/Δ32 CD4+ U87 cells were resistant to HIV infection. In conclusion, engineered CCR5Δ32/Δ32 mutations endowed CD4+ U87 cells with resistance against HIV‑1 infection; this site‑specific, size‑controlled and homozygous DNA deletion technique was able to induce precise genomic editing, i.e., the deletion or insertion of a predetermined length of DNA sequence at a specific locus throughout the genome.

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January 2018
Volume 17 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

2016 Impact Factor: 1.692
Ranked #19/128 Medicine Research and Experimental
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APA
Yu, A.Q., Ding, Y., Lu, Z.Y., Hao, Y.Z., Teng, Z.P., Yan, S.R. ... Zeng, Y. (2018). TALENs-mediated homozygous CCR5Δ32 mutations endow CD4+ U87 cells with resistance against HIV‑1 infection. Molecular Medicine Reports, 17, 243-249. https://doi.org/10.3892/mmr.2017.7889
MLA
Yu, A. Q., Ding, Y., Lu, Z. Y., Hao, Y. Z., Teng, Z. P., Yan, S. R., Li, D. S., Zeng, Y."TALENs-mediated homozygous CCR5Δ32 mutations endow CD4+ U87 cells with resistance against HIV‑1 infection". Molecular Medicine Reports 17.1 (2018): 243-249.
Chicago
Yu, A. Q., Ding, Y., Lu, Z. Y., Hao, Y. Z., Teng, Z. P., Yan, S. R., Li, D. S., Zeng, Y."TALENs-mediated homozygous CCR5Δ32 mutations endow CD4+ U87 cells with resistance against HIV‑1 infection". Molecular Medicine Reports 17, no. 1 (2018): 243-249. https://doi.org/10.3892/mmr.2017.7889