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Transduction

Transduction is the process by which DNA is transferred from one bacterium to another by a virus.^[1] It also refers to the process whereby foreign DNA is introduced into another cell via a viral vector. Transduction does not require physical contact between the cell donating the DNA and the cell receiving the DNA (which occurs in conjugation), and it is DNase resistant (transformation is susceptible to DNase). Transduction is a common tool used by molecular biologists to stably introduce a foreign gene into a host cell's genome.

When bacteriophages (viruses that infect bacteria) infect a bacterial cell, their normal mode of reproduction is to harness the replicational, transcriptional, and translation machinery of the host bacterial cell to make numerous virions, or complete viral particles, including the viral DNA or RNA and the protein coat.

Lytic and lysogenic (temperate) cycles

Transduction happens through either the lytic cycle or the lysogenic cycle. If the lysogenic cycle is adopted, the phage chromosome is integrated (by covalent bonds) into the bacterial chromosome, where it can remain dormant for thousands of generations. If the lysogen is induced (by UV light for example), the phage genome is excised from the bacterial chromosome and initiates the lytic cycle, which culminates in lysis of the cell and the release of phage particles. The lytic cycle leads to the production of new phage particles which are released by lysis of the host.

Transduction as a method for transferring genetic material

The packaging of bacteriophage DNA has low fidelity and small pieces of bacterial DNA, together with the bacteriophage genome, may become packaged into the bacteriophage genome. At the same time, some phage genes are left behind in the bacterial chromosome.

There are generally three types of recombination events that can lead to this incorporation of bacterial DNA into the viral DNA, leading to two modes of recombination.

Generalized transduction

Generalized transduction is the process by which any bacterial gene may be transferred to another bacterium via a bacteriophage, and typically carries only bacterial DNA and no viral DNA. In essence, this is the packaging of bacterial DNA into a viral envelope. This may occur in two main ways, recombination and headful packaging.

If bacteriophages undertake the lytic cycle of infection upon entering a bacterium, the virus will take control of the cell’s machinery for use in replicating its own viral DNA. If by chance bacterial chromosomal DNA is inserted into the viral capsid which is usually used to encapsulate the viral DNA, the mistake will lead to generalized transduction.

If the virus replicates using 'headful packaging', it attempts to fill the nucleocapsid with genetic material. If the viral genome results in spare capacity, viral packaging mechanisms may incorporate bacterial genetic material into the new virion.

The new virus capsule now loaded with part bacterial DNA continues to infect another bacterial cell. This bacterial material may become recombined into another bacterium upon infection.

When the new DNA is inserted into this recipient cell it can fall to one of three fates

The DNA will be absorbed by the cell and be recycled for spare parts.
If the DNA was originally a plasmid, it will re-circularize inside the new cell and become a plasmid again.
If the new DNA matches with a homologous region of the recipient cell’s chromosome, it will exchange DNA material similar to the actions in bacterial recombination.

Specialized transduction

Specialized transduction is the process by which a restricted set of bacterial genes is transferred to another bacterium. The genes that get transferred (donor genes) depend on where the phage genome is located on the chromosome. Specialized transduction occurs when the prophage excises imprecisely from the chromosome so that bacterial genes lying adjacent to the prophage are included in the excised DNA. The excised DNA is then packaged into a new virus particle, which then delivers the DNA to a new bacterium, where the donor genes can be inserted into the recipient chromosome or remain in the cytoplasm, depending on the nature of the bacteriophage.

When the partially encapsulated phage material infects another cell and becomes a "prophage" (is covalently bonded into the infected cell's chromosome), the partially coded prophage DNA is called a "heterogenote".

Example of specialized transduction is λ phages in Escherichia coli discovered by Esther Lederberg.^[2]^[3]

Medical Applications

Resistance to anti-biotic drugs
Correcting genetic diseases by direct modification of genetic errors

RNA, DNA

Viruses with RNA genomes cannot package DNA.

Upon lysis of the host cell, the mispackaged virions containing bacterial DNA can attach to other bacterial cells and inject the DNA they have packaged, thus transferring bacterial DNA from one cell to another. This DNA can become part of the new bacterium's genome and thus be stably inherited.

More general uses of the term

More generally, transduction is the process by which genetic material, e.g. DNA or siRNA, is inserted into a cell by a virus.

Common techniques in molecular biology are the use of viral vectors (including bacteriophages), electroporation, or chemical reagents that increase cell permeability. Transfection and transformation are also common ways to insert DNA into a cell.

Discovery

Transduction was discovered by Norton Zinder and Joshua Lederberg at the University of Wisconsin–Madison in 1951.^[4]

References

^ Jones, Elizabeth; Hartl, Daniel L. (1998). Genetics: principles and analysis. Boston: Jones and Bartlett Publishers. ISBN 0-7637-0489-X.
^ http://www.estherlederberg.com/Censorship/CensorshipIndex.html, click on Lambda Phage
^ http://www.estherlederberg.com/Papers.html; see publication #8
^ http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=iga.section.1363

External links

Genetic Transduction at the US National Library of Medicine Medical Subject Headings (MeSH)
Overview at ncbi.nlm.nih.gov
http://www.med.umich.edu/vcore/protocols/RetroviralCellScreenInfection13FEB2006.pdf (transduction protocol)
Generalized and Specialized transduction at sdsu.edu

English Journal

Histone deacetylase inhibition rescues gene knockout levels achieved with integrase-defective lentiviral vectors encoding zinc-finger nucleases.

Pelascini LP, Maggio I, Liu J, Holkers M, Cathomen T, Gonçalves MA.Author information 1 Department of Molecular Cell Biology, Leiden University Medical Center , 2333 ZC Leiden, The Netherlands .AbstractAbstract Zinc-finger nucleases (ZFNs) work as dimers to induce double-stranded DNA breaks (DSBs) at predefined chromosomal positions. In doing so, they constitute powerful triggers to edit and to interrogate the function of genomic sequences in higher eukaryotes. A preferred route to introduce ZFNs into somatic cells relies on their cotransduction with two integrase-defective lentiviral vectors (IDLVs) each encoding a monomer of a functional heterodimeric pair. The episomal nature of IDLVs diminishes the risk of genotoxicity and ensures the strict transient expression profile necessary to minimize deleterious effects associated with long-term ZFN activity. However, by deploying IDLVs and conventional lentiviral vectors encoding HPRT1- or eGFP-specific ZFNs, we report that DSB formation at target alleles is limited after IDLV-mediated ZFN transfer. This IDLV-specific underperformance stems, to a great extent, from the activity of chromatin-remodeling histone deacetylases (HDACs). Importantly, the prototypic and U.S. Food and Drug Administration-approved inhibitors of metal-dependent HDACs, trichostatin A and vorinostat, respectively, did not hinder illegitimate recombination-mediated repair of targeted chromosomal DSBs. This allowed rescuing IDLV-mediated site-directed mutagenesis to levels approaching those achieved by using their isogenic chromosomally integrating counterparts. Hence, HDAC inhibition constitutes an efficacious expedient to incorporate in genome-editing strategies based on transient IDLV-mediated ZFN expression. Finally, we compared two of the most commonly used readout systems to measure targeted gene knockout activities based on restriction and mismatch-sensitive endonucleases. These experiments indicate that these enzymatic assays display a similar performance.
Human gene therapy methods.Hum Gene Ther Methods.2013 Dec;24(6):399-411. doi: 10.1089/hgtb.2013.107. Epub 2013 Oct 29.
Abstract Zinc-finger nucleases (ZFNs) work as dimers to induce double-stranded DNA breaks (DSBs) at predefined chromosomal positions. In doing so, they constitute powerful triggers to edit and to interrogate the function of genomic sequences in higher eukaryotes. A preferred route to introduce ZFNs
PMID 24059449

Dual reporter gene imaging for tracking macrophage migration using the human sodium iodide symporter and an enhanced firefly luciferase in a murine inflammation model.

Lee HW, Jeon YH, Hwang MH, Kim JE, Park TI, Ha JH, Lee SW, Ahn BC, Lee J.Author information Department of Nuclear Medicine, School of Medicine, Kyungpook National University, 50 Samduk 2-ga, Daegu, 700-721, Republic of Korea, howonlee1234@gmail.com.AbstractPURPOSE: The purpose of this study is to visualize the migration of reporter macrophages expressing both the human sodium iodide symporter (hNIS) and enhanced firefly luciferase (effluc) gene in mice with chemically induced inflammation.
Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging.Mol Imaging Biol.2013 Dec;15(6):703-12. doi: 10.1007/s11307-013-0645-8.
PURPOSE: The purpose of this study is to visualize the migration of reporter macrophages expressing both the human sodium iodide symporter (hNIS) and enhanced firefly luciferase (effluc) gene in mice with chemically induced inflammation.PROCEDURES: A macrophage cell line expressing both hNIS and eff
PMID 23677652

Zinc finger nuclease-expressing baculoviral vectors mediate targeted genome integration of reprogramming factor genes to facilitate the generation of human induced pluripotent stem cells.

Phang RZ, Tay FC, Goh SL, Lau CH, Zhu H, Tan WK, Liang Q, Chen C, Du S, Li Z, Tay JC, Wu C, Zeng J, Fan W, Toh HC, Wang S.Author information Department of Biological Sciences, National University of Singapore, Singapore.AbstractIntegrative gene transfer using retroviruses to express reprogramming factors displays high efficiency in generating induced pluripotent stem cells (iPSCs), but the value of the method is limited because of the concern over mutagenesis associated with random insertion of transgenes. Site-specific integration into a preselected locus by engineered zinc-finger nuclease (ZFN) technology provides a potential way to overcome the problem. Here, we report the successful reprogramming of human fibroblasts into a state of pluripotency by baculoviral transduction-mediated, site-specific integration of OKSM (Oct3/4, Klf4, Sox2, and c-myc) transcription factor genes into the AAVS1 locus in human chromosome 19. Two nonintegrative baculoviral vectors were used for cotransduction, one expressing ZFNs and another as a donor vector encoding the four transcription factors. iPSC colonies were obtained at a high efficiency of 12% (the mean value of eight individual experiments). All characterized iPSC clones carried the transgenic cassette only at the ZFN-specified AAVS1 locus. We further demonstrated that when the donor cassette was flanked by heterospecific loxP sequences, the reprogramming genes in iPSCs could be replaced by another transgene using a baculoviral vector-based Cre recombinase-mediated cassette exchange system, thereby producing iPSCs free of exogenous reprogramming factors. Although the use of nonintegrating methods to generate iPSCs is rapidly becoming a standard approach, methods based on site-specific integration of reprogramming factor genes as reported here hold the potential for efficient generation of genetically amenable iPSCs suitable for future gene therapy applications.
Stem cells translational medicine.Stem Cells Transl Med.2013 Dec;2(12):935-45. doi: 10.5966/sctm.2013-0043. Epub 2013 Oct 28.
Integrative gene transfer using retroviruses to express reprogramming factors displays high efficiency in generating induced pluripotent stem cells (iPSCs), but the value of the method is limited because of the concern over mutagenesis associated with random insertion of transgenes. Site-specific in
PMID 24167318

Japanese Journal

Enhanced HER-2/neu-specific antitumor immunity by cotransduction of mouse dendritic cells with two genes encoding HER-2/neu and alpha tumor necrosis factor

CHEN Z.
Cancer Gene Ther. 9, 778-786, 2002
NAID 30014089602

Behavioral recovery in 6-hydroxydopaminelesioned rats by cotransduction of striatum with tyrosine hydroxylase and aromatic L-amino acid decarboxylase genes using two separate adeno-associated virus vectors

FAN D.
Human Gene Therapy 9, 2527-2535, 1998
NAID 80010701779

Behavioral recovery in 6-hydroxydopamine-lesioned rats by cotransduction of striatum with tyrosine hydroxylase and aromatic L-amino acid decarboxylase genes using two separate adeno-associated virus vectors