Oleg E Tolmachov, PhD, MA - Imperial College London

Oleg E Tolmachov

PhD, MA

Imperial College London

United Kingdom

ORCID logohttps://orcid.org/0000-0002-6926-4229

Oleg E Tolmachov, PhD, MA - Imperial College London

Oleg E Tolmachov

PhD, MA

Introduction

Primary Affiliation: Imperial College London - United Kingdom

Education

Nov 2013
St Mary's University Twickenham London, UK
MA in Bioethics and Medical Law
Dec 2007
Open University, UK
BA (Hon) in Mathematics
Apr 1992
Institute for Genetics and Selection of Industrial Microorganisms, Moscow, Russia
PhD in Genetics
Jun 1984
Moscow State University named after M.V. Lomonosov, Moscow, USSR
BSc (Hon) in Biology with Genetics

Publications

28Publications

190Reads

11Profile Views

114PubMed Central Citations

Shielding of non-target cells using RNA vectors conferring gene transfer resistance: A strategy to enhance targeting accuracy and reduce side-effects in therapeutic gene delivery.

Authors:
Oleg E Tolmachov

Med Hypotheses 2019 Jul 25;132:109328. Epub 2019 Jul 25.

Imperial College London, London, United Kingdom. Electronic address:

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http://dx.doi.org/10.1016/j.mehy.2019.109328DOI Listing
July 2019
8 Reads
1.152 Impact Factor

Transgenic DNA modules with pre-programmed self-destruction: Universal molecular devices to escape 'genetic litter' in gene and cell therapy.

Authors:
Oleg E Tolmachov

Med Hypotheses 2015 Nov 22;85(5):686-9. Epub 2015 Aug 22.

Section of Molecular Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom. Electronic address:

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http://dx.doi.org/10.1016/j.mehy.2015.08.012DOI Listing
November 2015
24 Reads
1.152 Impact Factor

Self-focusing therapeutic gene delivery with intelligent gene vector swarms: intra-swarm signalling through receptor transgene expression in targeted cells.

Authors:
Oleg E Tolmachov

Artif Intell Med 2015 Jan 17;63(1):1-6. Epub 2014 Dec 17.

Section of Molecular Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom. Electronic address:

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http://dx.doi.org/10.1016/j.artmed.2014.11.001DOI Listing
January 2015
18 Reads
1 Citation
2.020 Impact Factor

Split vector systems for ultra-targeted gene delivery: a contrivance to achieve ethical assurance of somatic gene therapy in vivo.

Authors:
Oleg E Tolmachov

Med Hypotheses 2014 Aug 2;83(2):211-6. Epub 2014 May 2.

Section of Molecular Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom. Electronic address:

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http://dx.doi.org/10.1016/j.mehy.2014.04.027DOI Listing
August 2014
2 Reads
1.152 Impact Factor

Hhex and Cer1 mediate the Sox17 pathway for cardiac mesoderm formation in embryonic stem cells.

Stem Cells 2014 Jun;32(6):1515-26

Center for Cardiovascular Development, Baylor College of Medicine, Houston, Texas, USA; Institute for Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas, USA.

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http://dx.doi.org/10.1002/stem.1695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260090PMC
June 2014
45 Reads
5 Citations
6.523 Impact Factor

Functional expression of Rab escort protein 1 following AAV2-mediated gene delivery in the retina of choroideremia mice and human cells ex vivo.

J Mol Med (Berl) 2013 Jul 12;91(7):825-37. Epub 2013 Jun 12.

Molecular Medicine Section, National Heart and Lung Institute, Imperial College London, London, SW7 2AZ, UK.

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http://dx.doi.org/10.1007/s00109-013-1006-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695676PMC
July 2013
18 Reads
22 Citations
5.110 Impact Factor

Self-entanglement of long linear DNA vectors using transient non-B-DNA attachment points: a new concept for improvement of non-viral therapeutic gene delivery.

Authors:
Oleg E Tolmachov

Med Hypotheses 2012 May 20;78(5):632-5. Epub 2012 Feb 20.

Cardiovascular Science, National Heart and Lung Institute, Imperial College London, Sir Alexander Fleming Building, Exhibition Road, London SW7 2AZ, UK.

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http://dx.doi.org/10.1016/j.mehy.2012.01.042DOI Listing
May 2012
2 Reads
2 Citations
1.152 Impact Factor

CHM/REP1 cDNA delivery by lentiviral vectors provides functional expression of the transgene in the retinal pigment epithelium of choroideremia mice.

J Gene Med 2012 Mar;14(3):158-68

Molecular Medicine Section, National Heart and Lung Institute, Imperial College London, London, UK.

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http://dx.doi.org/10.1002/jgm.1652DOI Listing
March 2012
3 Reads
15 Citations
2.472 Impact Factor

Building mosaics of therapeutic plasmid gene vectors.

Authors:
Oleg E Tolmachov

Curr Gene Ther 2011 Dec;11(6):466-78

Cardiovascular Science, National Heart and Lung Institute, Imperial College London, London, UK.

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December 2011
1 Read
3 Citations
2.542 Impact Factor

Development of S/MAR minicircles for enhanced and persistent transgene expression in the mouse liver.

J Mol Med (Berl) 2011 May 8;89(5):515-29. Epub 2011 Feb 8.

Gene Therapy Research Group, Section of Molecular Medicine, National Heart and Lung Institute, Imperial College London, London, UK.

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http://dx.doi.org/10.1007/s00109-010-0713-3DOI Listing
May 2011
24 Reads
13 Citations
5.110 Impact Factor

Tightly-wound miniknot vectors for gene therapy: a potential improvement over supercoiled minicircle DNA.

Authors:
Oleg E Tolmachov

Med Hypotheses 2010 Apr 13;74(4):702-4. Epub 2009 Nov 13.

Sir Alexander Fleming Building, National Heart and Lung Institute, Imperial College London, Exhibition Road, London SW7 2AZ, UK.

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http://dx.doi.org/10.1016/j.mehy.2009.10.035DOI Listing
April 2010
2 Reads
2 Citations
1.152 Impact Factor

Designing plasmid vectors.

Authors:
Oleg Tolmachov

Methods Mol Biol 2009 ;542:117-29

National Heart and Lung Institute, Faculty of Medicine, Imperial College London, South Kensington, London, UK.

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http://dx.doi.org/10.1007/978-1-59745-561-9_6DOI Listing
July 2009
13 Reads
3 Citations

Covalent attachment of multifunctional chimeric terminal proteins to 5' DNA ends: A potential new strategy for assembly of synthetic therapeutic gene vectors.

Med Hypotheses 2007 25;68(2):328-31. Epub 2006 Sep 25.

Section of Molecular and Cellular Medicine, Division of Biomedical Sciences, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, Exhibition Road, London SW7 2AZ, UK.

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http://dx.doi.org/10.1016/j.mehy.2006.06.055DOI Listing
April 2007
4 Reads
3 Citations
1.152 Impact Factor

A heterologous system for assembly of retroviral gene vectors: intracellular budding in yeast?

Authors:
Oleg Tolmachov

Med Hypotheses 2006 8;67(4):807-9. Epub 2006 Jun 8.

Section of Molecular and Cellular Medicine, Division of Biomedical Sciences, Faculty of Natural Sciences, Imperial College London, Sir Alexander Fleming Building, Exhibition Road, South Kensington, London SW7 2AZ, UK.

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http://dx.doi.org/10.1016/j.mehy.2006.04.017DOI Listing
October 2006
1 Read
1.152 Impact Factor

Overexpression of connexin 43 using a retroviral vector improves electrical coupling of skeletal myoblasts with cardiac myocytes in vitro.

BMC Cardiovasc Disord 2006 6;6:25. Epub 2006 Jun 6.

BMC Cardiovasc Disord

Organ transplantation is presently often the only available option to repair a damaged heart. As heart donors are scarce, engineering of cardiac grafts from autologous skeletal myoblasts is a promising novel therapeutic strategy. The functionality of skeletal muscle cells in the heart milieu is, however, limited because of their inability to integrate electrically and mechanically into the myocardium. Therefore, in pursuit of improved cardiac integration of skeletal muscle grafts we sought to modify primary skeletal myoblasts by overexpression of the main gap-junctional protein connexin 43 and to study electrical coupling of connexin 43 overexpressing myoblasts to cardiac myocytes in vitro.
To create an efficient means for overexpression of connexin 43 in skeletal myoblasts we constructed a bicistronic retroviral vector MLV-CX43-EGFP expressing the human connexin 43 cDNA and the marker EGFP gene. This vector was employed to transduce primary rat skeletal myoblasts in optimised conditions involving a concomitant use of the retrovirus immobilising protein RetroNectin and the polycation transduction enhancer Transfectam. The EGFP-positive transduced cells were then enriched by flow cytometry.
More than four-fold overexpression of connexin 43 in the transduced skeletal myoblasts, compared with non-transduced cells, was shown by Western blotting. Functionality of the overexpressed connexin 43 was demonstrated by microinjection of a fluorescent dye showing enhanced gap-junctional intercellular transfer in connexin 43 transduced myoblasts compared with transfer in non-transduced myoblasts. Rat cardiac myocytes were cultured in multielectrode array culture dishes together with connexin 43/EGFP transduced skeletal myoblasts, control non-transduced skeletal myoblasts or alone. Extracellular field action potential activation rates in the co-cultures of connexin 43 transduced skeletal myoblasts with cardiac myocytes were significantly higher than in the co-cultures of non-transduced skeletal myoblasts with cardiac myocytes and similar to the rates in pure cultures of cardiac myocytes.
The observed elevated field action potential activation rate in the co-cultures of cardiac myocytes with connexin 43 transduced skeletal myoblasts indicates enhanced cell-to-cell electrical coupling due to overexpression of connexin 43 in skeletal myoblasts. This study suggests that retroviral connexin 43 transduction can be employed to augment engineering of the electrocompetent cardiac grafts from patients' own skeletal myoblasts.

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July 2006
2 Reads

Nuclear-targeted minicircle to enhance gene transfer with non-viral vectors in vitro and in vivo.

J Gene Med 2006 Jun;8(6):754-63

J Gene Med

To develop more efficient non-viral vectors, we have previously described a novel approach to attach a nuclear localisation signal (NLS) to plasmid DNA, by generating a fusion protein between the tetracycline repressor protein TetR and an SV40 NLS peptide (TetR-NLS). The high affinity of TetR for the DNA sequence tetO is used to bind the NLS to DNA. We have now investigated the ability of this system displaying the SV40 NLS or HIV-1 TAT peptide to enhance nuclear import of a minimised DNA construct more suitable for in vivo gene delivery: a minicircle.
We have produced a new LacZ minicircle compatible with the TetR system. After transfection of the minicircle in combination with TetR-NLS or TetR-TAT using different transfection agents, we first measured beta-galactosidase activity in vitro. We then used a special delivery technique, in which DOTAP/cholesterol liposomes and DNA/protein complexes are sequentially injected intravenously, to evaluate the activity of this system in vivo.
In vitro results showed a 30-fold increase in transfection efficiency of the nuclear-targeted minicircle compared to normal plasmid lipofection. Results on cell cycle arrested cells seem to indicate a different mechanism between the TetR-NLS and TetR-TAT. Finally, we demonstrate a more than 6-fold increase in beta-galactosidase expression in the mouse lung using the minicircle and the TetR-TAT protein. This increase is specific for the peptide sequence and is not observed with the control protein TetR.
Our results indicate that the combination of a minicircle DNA construct with a TetR nuclear-targeting system is able to potentiate gene expression of non-viral vectors.

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June 2006
2 Reads

RecET driven chromosomal gene targeting to generate a RecA deficient Escherichia coli strain for Cre mediated production of minicircle DNA.

BMC Biotechnol 2006 Mar 10;6:17. Epub 2006 Mar 10.

Division of Biomedical Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, UK.

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http://dx.doi.org/10.1186/1472-6750-6-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1421399PMC
March 2006
2 Reads
2 Citations
2.034 Impact Factor

Coupled analysis of bacterial transformants and ligation mixture by duplex PCR enables detection of fatal instability of a nascent recombinant plasmid.

J Biochem Biophys Methods 2005 Aug;64(2):142-6

Section of Cell and Molecular Biology, Faculty of Medicine, 2nd floor, Sir Alexander Fleming Building, Imperial College London, London SW7 2AZ, UK.

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http://dx.doi.org/10.1016/j.jbbm.2005.04.008DOI Listing
August 2005
3 Reads
1 Citation

Accurate size gauging of ExoIII/S1-generated deletions by PCR analysis of ligation mixtures.

Anal Biochem 2005 Apr;339(2):348-50

Cell and Molecular Biology Section, Biomedical Sciences Division, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK.

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http://dx.doi.org/10.1016/j.ab.2004.11.008DOI Listing
April 2005
1 Read
2.220 Impact Factor

Development of a self-assembling nuclear targeting vector system based on the tetracycline repressor protein.

J Biol Chem 2004 Feb 7;279(7):5555-64. Epub 2003 Nov 7.

Gene Therapy Research Group, Division of Biomedical Science, Imperial College London, Sir Alexander Fleming Building, Exhibition Road, London SW7 2AZ, United Kingdom.

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http://dx.doi.org/10.1074/jbc.M311894200DOI Listing
February 2004
5 Reads
6 Citations
4.573 Impact Factor

An araC-controlled bacterial cre expression system to produce DNA minicircle vectors for nuclear and mitochondrial gene therapy.

J Biol Chem 2001 Jun 13;276(25):23018-27. Epub 2001 Apr 13.

Cystic Fibrosis Gene Therapy Group, Division of Biomedical Sciences, SAF Bldg., Imperial College of Science, Technology and Medicine, Exhibition Rd., London SW7 2AZ, United Kingdom.

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http://dx.doi.org/10.1074/jbc.M010873200DOI Listing
June 2001
4 Reads
33 Citations
4.573 Impact Factor

Introduction of chloramphenicol resistance into the modified mouse mitochondrial genome: cloning of unstable sequences by passage through yeast.

Anal Biochem 2000 Jan;277(2):236-42

Cystic Fibrosis Gene Therapy Research Group, Section of Molecular Genetics, Division of Biomedical Sciences, Imperial College School of Medicine, Sir Alexander Fleming Building, South Kensington, London, SW7 2AZ, United Kingdom.

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http://dx.doi.org/10.1006/abio.1999.4382DOI Listing
January 2000
1 Read
3 Citations
2.220 Impact Factor

Cloning Based on Efficient Three-Fragment Assembly DNA Ligation

Biochemica 1998 (3): 29-30

Biochemica

The efficiency of the Rapid DNA Ligation Kit from Roche Molecular Biochemicals was compared with standard and optimized conventional ligation procedures. The reactions generated circular recombinant bacteriophage DNA in a three-fragment assembly DNA ligation. Sequential blunt-end and cohesive-end ligation, including a temperature shift from 26°C to 14°C, led to a more than 10-fold increase in the number of transformants obtained. Applying a modified protocol, the kit was found to provide a reliable, fast, and remarkably efficient procedure for this complex application.

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July 1998
2 Reads

Selection of mutations in Corynebacterium glutamicum aspartate kinase genes using a cosmid vector and specific phage-resistant Brevibacterium flavum mutant

Genetika 1993 29(8):1246-1255.

Genetika

Corynebacterium glutamicum aspartate kinase genes (LysC-alpha and LysC-beta) were cloned in Brevibacterium flavum using a multicopy cosmid vector pCLF3 with a cos sequence of B. flavum phage BBL1. Amplification of genes LysC-alpha-beta led to: (I) 12-fold increase in the aspartate kinase activity: (II) appearance of lysine in the bacterial culture medium after fermentation; (III) bacterial resistance to the lysine analogue S-(2-aminoethyl)-L-cysteine (AEC). Mutations were obtained in the cloned aspartate kinase genes which increased bacterial resistance to AEC and increased lysine secretion in the culture medium. The data proved that the aspartate kinase from C. glutamicum 77 strain was sensitive to inhibition by lysine and threonine, while the mutant aspartate kinase was not. To select mutations in the cloned lysC-alpha-beta genes, cosmid transduction in the phage-resistant strain B. flavum ST21 was performed and the AEC-resistant transductants were selected. Amplification of C. glutamicum 77 aspartate kinase genes led to statistically valid increase in lysine production by the producer strain Brevibacterium sp. E531.

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August 1993
3 Reads

[Study of phage BBL1 of Brevibacterium flavum and construction of a plasmid containing the cos-sequence of BBL1].

Mol Gen Mikrobiol Virusol 1992 (1-2):18-23

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August 1992
6 Reads

[Potential vectors for molecular cloning in Brevibacterium flavum].

Mol Gen Mikrobiol Virusol 1991 Nov(11):3-8

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November 1991
2 Reads

[Study of Brevibacterium flavum phage PhiBSh6].

Mol Gen Mikrobiol Virusol 1991 Oct(10):8-12

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October 1991
1 Read

Top co-authors

Charles Coutelle
Charles Coutelle

National Heart and Lung Institute

6
Brian Bigger
Brian Bigger

University of Manchester

2
Tanya Tolmachova
Tanya Tolmachova

National Heart and Lung Institute

2
Miguel C Seabra
Miguel C Seabra

Imperial College London

2
Michael Themis
Michael Themis

Brunel University

2
Richard P Harbottle
Richard P Harbottle

3 German Cancer Research Center (DKFZ)

1
Marcello Niceta
Marcello Niceta

Dipartimento di Ematologia

1