ArticleProceedings of the National Academy of Sciences of the United States of America2011
Human artificial chromosome (HAC) vector with a conditional centromere for correction of genetic deficiencies in human cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
54 citing papers in PubMed.
- HSP90 inhibition disrupts telomere maintenance and promotes chromosomal instability (CIN) in cancer cells.Research square · 2026Article
- Synthetic rewriting technologies in mammalian cells.Nature communications · 2026Review
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- The lives of cells, recorded.Nature reviews. Genetics · 2025Review
- Therapy enhancing chromosome instability may be advantageous forNAR cancer · 2025Article
- Comparative analysis and classification of highly divergent mouse rDNA units based on their intergenic spacer (IGS) variability.NAR genomics and bioinformatics · 2024Article
- Review
- Actively transcribed rDNA and distal junction (DJ) sequence are involved in association of NORs with nucleoli.Cellular and molecular life sciences : CMLS · 2023Article
- Introduction of a long synthetic repetitive DNA sequence into cultured tobacco cells.Plant biotechnology (Tokyo, Japan) · 2022Article
- Assembly of Multiple Full-Size Genes or Genomic DNA Fragments on Human Artificial Chromosomes Using the Iterative Integration System.Current protocols · 2021Article
- Highly Efficient Microcell-Mediated Transfer of HACs Containing a Genomic Region of Interest into Mammalian Cells.Current protocols · 2021Article
- Highly Selective, CRISPR/Cas9-Mediated Isolation of Genes and Genomic Loci from Complex Genomes by TAR Cloning in Yeast.Current protocols · 2021Article
- Terpyridine platinum compounds induce telomere dysfunction and chromosome instability in cancer cells.Oncotarget · 2021Article
- Pluripotent stem cell-based gene therapy approach: human de novo synthesized chromosomes.Cellular and molecular life sciences : CMLS · 2021Review
- Analysis of Complex DNA Rearrangements during Early Stages of HAC Formation.ACS synthetic biology · 2020Article
- Human AlphoidCells · 2020Article
- Genetic and epigenetic effects on centromere establishment.Chromosoma · 2020Review
- Rhodopsin Genomic Loci DNA Nanoparticles Improve Expression and Rescue of Retinal Degeneration in a Model for Retinitis Pigmentosa.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- A novel assay to screen siRNA libraries identifies protein kinases required for chromosome transmission.Genome research · 2019Article
- TAR Cloning: Perspectives for Functional Genomics, Biomedicine, and Biotechnology.Molecular therapy. Methods & clinical development · 2019Review
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Authors and funding
12 authors.
Funding
Abstract
Human artificial chromosome (HAC)-based vectors offer a promising system for delivery and expression of full-length human genes of any size. HACs avoid the limited cloning capacity, lack of copy number control, and insertional mutagenesis caused by integration into host chromosomes that plague viral vectors. We previously described a synthetic HAC that can be easily eliminated from cell populations by inactivation of its conditional kinetochore. Here, we demonstrate the utility of this HAC, which has a unique gene acceptor site, for delivery of full-length genes and correction of genetic deficiencies in human cells. A battery of functional tests was performed to demonstrate expression of NBS1 and VHL genes from the HAC at physiological levels. We also show that phenotypes arising from stable gene expression can be reversed when cells are "cured" of the HAC by inactivating its kinetochore in proliferating cell populations, a feature that provides a control for phenotypic changes attributed to expression of HAC-encoded genes. This generation of human artificial chromosomes should be suitable for studies of gene function and therapeutic applications.
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