ArticlePloS one2014
Novel method to load multiple genes onto a mammalian artificial chromosome.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Reconstitution of DNA fragments on HAC/MAC via the fragment-assembly system.Scientific reports · 2026Article
- 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
- TAR Cloning: Perspectives for Functional Genomics, Biomedicine, and Biotechnology.Molecular therapy. Methods & clinical development · 2019Review
- Engineering Synthetic Chromosomes by Sequential Loading of Multiple Genomic Payloads over 100 Kilobase Pairs in Size.Molecular therapy. Methods & clinical development · 2019Article
- Human Artificial Chromosome with Regulated Centromere: A Tool for Genome and Cancer Studies.ACS synthetic biology · 2018Review
- Method to Assemble Genomic DNA Fragments or Genes on Human Artificial Chromosome with Regulated Kinetochore Using a Multi-Integrase System.ACS synthetic biology · 2018Article
- Moving toward a higher efficiency of microcell-mediated chromosome transfer.Molecular therapy. Methods & clinical development · 2016Article
- A pathway from chromosome transfer to engineering resulting in human and mouse artificial chromosomes for a variety of applications to bio-medical challenges.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2015Review
- De novo formed satellite DNA-based mammalian artificial chromosomes and their possible applications.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2015Review
- Human artificial chromosomes for future biomedicine.Cell cycle (Georgetown, Tex.) · 2015Article
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Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mammalian artificial chromosomes are natural chromosome-based vectors that may carry a vast amount of genetic material in terms of both size and number. They are reasonably stable and segregate well in both mitosis and meiosis. A platform artificial chromosome expression system (ACEs) was earlier described with multiple loading sites for a modified lambda-integrase enzyme. It has been shown that this ACEs is suitable for high-level industrial protein production and the treatment of a mouse model for a devastating human disorder, Krabbe's disease. ACEs-treated mutant mice carrying a therapeutic gene lived more than four times longer than untreated counterparts. This novel gene therapy method is called combined mammalian artificial chromosome-stem cell therapy. At present, this method suffers from the limitation that a new selection marker gene should be present for each therapeutic gene loaded onto the ACEs. Complex diseases require the cooperative action of several genes for treatment, but only a limited number of selection marker genes are available and there is also a risk of serious side-effects caused by the unwanted expression of these marker genes in mammalian cells, organs and organisms. We describe here a novel method to load multiple genes onto the ACEs by using only two selectable marker genes. These markers may be removed from the ACEs before therapeutic application. This novel technology could revolutionize gene therapeutic applications targeting the treatment of complex disorders and cancers. It could also speed up cell therapy by allowing researchers to engineer a chromosome with a predetermined set of genetic factors to differentiate adult stem cells, embryonic stem cells and induced pluripotent stem (iPS) cells into cell types of therapeutic value. It is also a suitable tool for the investigation of complex biochemical pathways in basic science by producing an ACEs with several genes from a signal transduction pathway of interest.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.