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The Publications

Foto: Johan Bävman
The MNM PI. Photo: Johan Bävman

 

AAV Production Everywhere: A Simple, Fast, and Reliable Protocol for In-house AAV Vector Production Based on Chloroform Extraction.

Negrini M, Wang G, Heuer A, Björklund T, Davidsson M.
Curr Protoc Neurosci. 2020 Sep;93(1):e103. doi: 10.1002/cpns.103.
PMID: 32865885

A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism.

Davidsson M, Wang G, Aldrin-Kirk P, Cardoso T, Nolbrant S, Hartnor M, Mudannayake J, Parmar M,Björklund T.
Proc Natl Acad Sci U S A. 2019 Dec 9;116(52):27053-62. doi: 10.1073/pnas.1910061116. 
PMID: 31818949

Seeding of protein aggregation causes cognitive impairment in rat model of cortical synucleinopathy.

Espa E, Clemensson EKH, Luk KC, Heuer A, Björklund T, Cenci MA.
Mov Disord. 2019 Nov;34(11):1699-1710. doi: 10.1002/mds.27810. Epub 2019 Aug 26.
PMID: 31449702

Vector-mediated l-3,4-dihydroxyphenylalanine delivery reverses motor impairments in a primate model of Parkinson's disease.

Rosenblad C, Li Q, Pioli EY, Dovero S, Antunes AS, Agúndez L, Bardelli M, Linden RM, Henckaerts E, Björklund A, Bezard E, Björklund T.
Brain. 2019 Aug 1;142(8):2402-2416. doi: 10.1093/brain/awz176.
PMID: 31243443

Practical Considerations for the Use of DREADD and Other Chemogenetic Receptors to Regulate Neuronal Activity in the Mammalian Brain.
Aldrin-Kirk P, Björklund T.
Methods Mol Biol. 2019;1937:59-87. doi: 10.1007/978-1-4939-9065-8_4.
PMID: 30706390

Molecular barcoding of viral vectors enables mapping and optimization of mRNA trans-splicing.
Davidsson M, Díaz-Fernández P, Torroba M, Schwich OD, Aldrin-Kirk P, Quintino L, Heuer A, Wang G, Lundberg C, Björklund T.
RNA. 2018 May;24(5):673-687. doi: 10.1261/rna.063925.117. Epub 2018 Jan 31.
PMID: 29386333

A novel adeno-associated virus capsid with enhanced neurotropism corrects a lysosomal transmembrane enzyme deficiency.
Tordo J, O'Leary C, Antunes ASLM, Palomar N, Aldrin-Kirk P, Basche M, Bennett A, D'Souza Z, Gleitz H, Godwin A, Holley RJ, Parker H, Liao AY, Rouse P, Youshani AS, Dridi L, Martins C, Levade T, Stacey KB, Davis DM, Dyer A, Clément N, Björklund T, Ali RR, Agbandje-McKenna M, Rahim AA, Pshezhetsky A, Waddington SN, Linden RM, Bigger BW, Henckaerts E.
Brain. 2018 Jul 1;141(7):2014-2031. doi: 10.1093/brain/awy126.
PMID: 29788236 

Repairing the Brain: Gene Therapy.
Björklund T.
J Parkinsons Dis. 2018;8(s1):S123-S130. doi: 10.3233/JPD-181485.
PMID: 30584164

Chemogenetic modulation of cholinergic interneurons reveals their regulating role on the direct and indirect output pathways from the striatum.
Aldrin-Kirk P, Heuer A, Ottosson DR, Davidsson M, Mattsson B, Björklund T.
Neurobiol Dis. 2018 Jan;109(Pt A):148-162. doi: 10.1016/j.nbd.2017.10.010. Epub 2017 Oct 14.
PMID: 29037828

A novel process of viral vector barcoding and library preparation enables high-diversity library generation and recombination-free paired-end sequencing
Davidsson M, Diaz-Fernandez M, Schwich OD, Torroba M, Wang G & Björklund T.
Scientific Reports. 2016 doi:10.1038/srep37563
PMID: 27874090

Cellular Barcoding Links B-1a B Cell Potential to a Fetal Hematopoietic Stem Cell State at the Single-Cell Level.
Kristiansen TA, Jaensson Gyllenbäck E, Zriwil A, Björklund T, Daniel JA, Sitnicka E, Soneji S, Bryder D, Yuan J.
Immunity. 2016 Aug 16;45(2):346-57. doi: 10.1016/j.immuni.2016.07.014.
PMID: 27533015

Identification of Multiple QTLs Linked to Neuropathology in the Engrailed-1 Heterozygous Mouse Model of Parkinson's Disease.
Kurowska Z, Jewett M, Brattås PL, Jimenez-Ferrer I, Kenéz X, Björklund T, Nordström U, Brundin P, Swanberg M.
Sci Rep. 2016 Aug 23;6:31701. doi: 10.1038/srep31701.
PMID: 27550741

DREADD Modulation of Transplanted DA Neurons Reveals a Novel Parkinsonian Dyskinesia Mechanism Mediated by the Serotonin 5-HT6 Receptor
Patrick Aldrin-Kirk, Andreas Heuer, Gang Wang, Bengt Mattsson, Martin Lundblad, Malin Parmar, Tomas Björklund
Neuron. 2016 Jun 1;90(5):955-68. doi: 10.1016/j.neuron.2016.04.017.
PMID: 27161524 

Expression of Multiple Functional RNAs or Proteins from One Viral Vector.
Björklund T.
Methods Mol Biol. 2016;1382:41-56. doi: 10.1007/978-1-4939-3271-9_3.
PMID: 26611577

Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats.
Holmqvist S, Chutna O, Bousset L, Aldrin-Kirk P, Li W, Björklund T, Wang ZY, Roybon L, Melki R, Li JY.
Acta Neuropathol. 2014 Dec;128(6):805-20. doi: 10.1007/s00401-014-1343-6. Epub 2014 Oct 9.
PMID: 25296989

Novel AAV-based rat model of forebrain synucleinopathy shows extensive pathologies and progressive loss of cholinergic interneurons.
Aldrin-Kirk P, Davidsson M, Holmqvist S, Li JY, Björklund T.
PLoS One. 2014 Jul 7;9(7):e100869. doi: 10.1371/journal.pone.0100869. eCollection 2014.
PMID: 24999658

Continuous DOPA synthesis from a single AAV: dosing and efficacy in models of Parkinson's disease.
Cederfjäll E, Nilsson N, Sahin G, Chu Y, Nikitidou E, Björklund T, Kordower JH, Kirik D.
Sci Rep. 2013;3:2157. doi: 10.1038/srep02157.
PMID: 23831692

A novel α-synuclein-GFP mouse model displays progressive motor impairment, olfactory dysfunction and accumulation of α-synuclein-GFP.
Hansen C, Björklund T, Petit GH, Lundblad M, Murmu RP, Brundin P, Li JY.
Neurobiol Dis. 2013 Aug;56:145-55. doi: 10.1016/j.nbd.2013.04.017. Epub 2013 Apr 30.
PMID: 23643841

Dysregulated dopamine storage increases the vulnerability to α-synuclein in nigral neurons.
Ulusoy A, Björklund T, Buck K, Kirik D.
Neurobiol Dis. 2012 Sep;47(3):367-77. doi: 10.1016/j.nbd.2012.05.012. Epub 2012 May 31.
PMID: 22659302 

Design of a single AAV vector for coexpression of TH and GCH1 to establish continuous DOPA synthesis in a rat model of Parkinson's disease.
Cederfjäll E, Sahin G, Kirik D, Björklund T.
Mol Ther. 2012 Jul;20(7):1315-26. doi: 10.1038/mt.2012.1. Epub 2012 Jan 31.
PMID: 22294150

Gene therapy for Parkinson's disease shows promise.
Björklund A, Björklund T.
Sci Transl Med. 2011 Apr 20;3(79):79ed1. doi: 10.1126/scitranslmed.3002430. No abstract available.
PMID: 21508307

Mutant huntingtin causes metabolic imbalance by disruption of hypothalamic neurocircuits.
Hult S, Soylu R, Björklund T, Belgardt BF, Mauer J, Brüning JC, Kirik D, Petersén Å.
Cell Metab. 2011 Apr 6;13(4):428-39. doi: 10.1016/j.cmet.2011.02.013.
PMID: 21459327

Gene therapy for dopamine replacement.
Björklund T, Cederfjäll EA, Kirik D.
Prog Brain Res. 2010;184:221-35. doi: 10.1016/S0079-6123(10)84012-9. Review.
PMID: 20887878

A general chemical method to regulate protein stability in the mammalian central nervous system.
Iwamoto M, Björklund T, Lundberg C, Kirik D, Wandless TJ.
Chem Biol. 2010 Sep 24;17(9):981-8. doi: 10.1016/j.chembiol.2010.07.009.
PMID: 20851347

Gene therapy for dopamine replacement in Parkinson's disease.
Björklund A, Björklund T, Kirik D.
Sci Transl Med. 2009 Oct 14;1(2):2ps2. doi: 10.1126/scitranslmed.3000350.
PMID: 20368161

Gene therapy for Parkinson's disease.
Bjorklund T, Kordower JH.
Mov Disord. 2010;25 Suppl 1:S161-73. doi: 10.1002/mds.22785. Review.
PMID: 20187249

Optimized adeno-associated viral vector-mediated striatal DOPA delivery restores sensorimotor function and prevents dyskinesias in a model of advanced Parkinson's disease.
Björklund T, Carlsson T, Cederfjäll EA, Carta M, Kirik D.
Brain. 2010 Feb;133(Pt 2):496-511. doi: 10.1093/brain/awp314. Epub 2010 Feb 2.
PMID: 20129936

Differential transduction following basal ganglia administration of distinct pseudotyped AAV capsid serotypes in nonhuman primates.
Dodiya HB, Bjorklund T, Stansell J 3rd, Mandel RJ, Kirik D, Kordower JH.
Mol Ther. 2010 Mar;18(3):579-87. doi: 10.1038/mt.2009.216. Epub 2009 Sep 22.
PMID: 19773746

Optimization of continuous in vivo DOPA production and studies on ectopic DA synthesis using rAAV5 vectors in Parkinsonian rats.
Björklund T, Hall H, Breysse N, Soneson C, Carlsson T, Mandel RJ, Carta M, Kirik D.
J Neurochem. 2009 Oct;111(2):355-67. doi: 10.1111/j.1471-4159.2009.06340.x. Epub 2009 Aug 17.
PMID: 19686242

Dose optimization for long-term rAAV-mediated RNA interference in the nigrostriatal projection neurons.
Ulusoy A, Sahin G, Björklund T, Aebischer P, Kirik D.
Mol Ther. 2009 Sep;17(9):1574-84. doi: 10.1038/mt.2009.142. Epub 2009 Jul 7.
PMID: 19584816

Scientific rationale for the development of gene therapy strategies for Parkinson's disease.
Björklund T, Kirik D.
Biochim Biophys Acta. 2009 Jul;1792(7):703-13. doi: 10.1016/j.bbadis.2009.02.009. Epub 2009 Feb 27. Review.
PMID: 19254760

Positron emission tomography imaging demonstrates correlation between behavioral recovery and correction of dopamine neurotransmission after gene therapy.
Leriche L, Björklund T, Breysse N, Besret L, Grégoire MC, Carlsson T, Dollé F, Mandel RJ, Déglon N, Hantraye P, Kirik D.
J Neurosci. 2009 Feb 4;29(5):1544-53. doi: 10.1523/JNEUROSCI.4491-08.2009.
PMID: 19193901

Applications of lentiviral vectors for biology and gene therapy of neurological disorders.
Lundberg C, Björklund T, Carlsson T, Jakobsson J, Hantraye P, Déglon N, Kirik D.
Curr Gene Ther. 2008 Dec;8(6):461-73. Review.
PMID: 19075629

In vivo gene delivery for development of mammalian models for Parkinson's disease.
Ulusoy A, Bjorklund T, Hermening S, Kirik D.
Exp Neurol. 2008 Jan;209(1):89-100. Epub 2007 Sep 22. Review.
PMID: 18028909

Restoration of the striatal dopamine synthesis for Parkinson's disease: viral vector-mediated enzyme replacement strategy.
Carlsson T, Björklund T, Kirik D.
Curr Gene Ther. 2007 Apr;7(2):109-20. Review.
PMID: 17430130

Long-term consequences of human alpha-synuclein overexpression in the primate ventral midbrain.
Eslamboli A, Romero-Ramos M, Burger C, Bjorklund T, Muzyczka N, Mandel RJ, Baker H, Ridley RM, Kirik D.
Brain. 2007 Mar;130(Pt 3):799-815. Epub 2007 Feb 15.
PMID: 17303591

Morphometric and psychometric comparisons between non-substance-abusing patients with posttraumatic stress disorder and normal controls.
Emdad R, Bonekamp D, Sondergaard HP, Bjorklund T, Agartz I, Ingvar M, Theorell T.
Psychother Psychosom. 2006;75(2):122-32.
PMID: 16508348

Imaging in cell-based therapy for neurodegenerative diseases.
Kirik D, Breysse N, Björklund T, Besret L, Hantraye P.
Eur J Nucl Med Mol Imaging. 2005 Dec;32 Suppl 2:S417-34. Review.
PMID: 16267643

Personal favorites

A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism.

Davidsson M, Wang G, Aldrin-Kirk P, Cardoso T, Nolbrant S, Hartnor M, Mudannayake J, Parmar M,Björklund T.
PNAS. 2019 Dec 9;116(52):27053-62.
PMID: 31818949

Vector-mediated l-3,4-dihydroxyphenylalanine delivery reverses motor impairments in a primate model of Parkinson's disease.

Rosenblad C, Li Q, Pioli EY, Dovero S, Antunes AS, Agúndez L, Bardelli M, Linden RM, Henckaerts E, Björklund A, Bezard E, Björklund T.
Brain. 2019 Aug 1;142(8):2402-2416.
PMID: 31243443 

A novel process of viral vector barcoding and library preparation enables high-diversity library generation and recombination-free paired-end sequencing
Davidsson M, Diaz-Fernandez M, Schwich OD, Torroba M, Wang G & Björklund T.
Scientific Reports. 2016 doi:10.1038/srep37563
PMID: 27874090

DREADD Modulation of Transplanted DA Neurons Reveals a Novel Parkinsonian Dyskinesia Mechanism Mediated by the Serotonin 5-HT6 Receptor
Patrick Aldrin-Kirk, Andreas Heuer, Gang Wang, Bengt Mattsson, Martin Lundblad, Malin Parmar, Tomas Björklund
Neuron (2016), http://dx.doi.org/10.1016/j.neuron.2016.04.017 

Novel AAV-based rat model of forebrain synucleinopathy shows extensive pathologies and progressive loss of cholinergic interneurons.
Aldrin-Kirk P, Davidsson M, Holmqvist S, Li JY, Björklund T.
PLoS One. 2014 Jul 7;9(7):e100869. doi: 10.1371/journal.pone.0100869. eCollection 2014.
PMID: 24999658

Design of a single AAV vector for coexpression of TH and GCH1 to establish continuous DOPA synthesis in a rat model of Parkinson's disease.
Cederfjäll E, Sahin G, Kirik D, Björklund T.
Mol Ther. 2012

Mutant huntingtin causes metabolic imbalance by disruption of hypothalamic neurocircuits.
Hult S, Soylu R, Björklund T, Belgardt BF, Mauer J, Brüning JC, Kirik D, Petersén Å.
Cell Metab. 2011

Gene therapy for Parkinson's disease shows promise.
Björklund A, Björklund T.
Sci Transl Med. 2011

Optimized adeno-associated viral vector-mediated striatal DOPA delivery restores sensorimotor function and prevents dyskinesias in a model of advanced Parkinson's disease.
Björklund T, Carlsson T, Cederfjäll EA, Carta M, Kirik D.
Brain. 2010

Cell therapy for Parkinson's disease has experienced substantial growth in the past decades with several ongoing clinica...
Transplantation in Parkinson's disease using human embryonic stem cell (hESC)-derived dopaminergic (DA) neurons is a pro...
Recent technological and conceptual advances have resulted in a plethora of exciting novel engineered adeno associated v...
Aggregation of α-synuclein is associated with neurodegeneration and a hallmark pathology in synucleinopathies. These agg...
Recent advances in cell reprogramming have made it possible to form new therapeutic cells within the body itself via a p...
Recombinant adeno-associated virus (rAAV) is a mammalian virus that has been altered to be used as a gene delivery vehic...
Adeno-associated virus (AAV) capsid modification enables the generation of recombinant vectors with tailored properties ...
CONCLUSIONS: Cortical overexpression of human α-synuclein is not sufficient to produce cognitive dysfunction, whereas co...
Ever since its introduction 40 years ago l-3,4-dihydroxyphenylalanine (l-DOPA) therapy has retained its role as the lead...
Chemogenetics is the process of genetically expressing a macromolecule receptor capable of modulating the activity of th...
In vivo gene therapy for neurodegenerative disorders has turned out to be a formidable challenge. It is a field not much...
Recombinant adeno-associated viruses (AAVs) are popular in vivo gene transfer vehicles. However, vector doses needed to ...
Genome editing has proven to be highly potent in the generation of functional gene knockouts in dividing cells. In the C...
The intricate balance between dopaminergic and cholinergic neurotransmission in the striatum has been thoroughly difficu...
Detailed characterization and mapping of oligonucleotide function in vivo is generally a very time consuming effort that...
Motor symptoms in Parkinson's disease are attributed to degeneration of midbrain dopaminergic neurons (DNs). Heterozygos...
Hematopoietic stem cells (HSCs) undergo a functional switch in neonatal mice hallmarked by a decrease in self-renewing d...
Transplantation of DA neurons is actively pursued as a restorative therapy in Parkinson's disease (PD). Pioneering clini...
In this chapter, we will cover the available design choices for enabling expression of two functional protein or RNA seq...
CONCLUSIONS: The ABDE showed an almost perfect agreement with a 21-radiologist panel in binary BD classification on a mu...
The cellular hallmarks of Parkinson's disease (PD) are the loss of nigral dopaminergic neurons and the formation of α-sy...
Synucleinopathies, characterized by intracellular aggregation of α-synuclein protein, share a number of features in path...
We used a single adeno-associated viral (AAV) vector co-expressing tyrosine hydroxylase (TH) and GTP cyclohydrolase 1 (G...
Compelling evidence suggests that accumulation and aggregation of alpha-synuclein (α-syn) contribute to the pathogenesis...
Impairments in the capacity of dopaminergic neurons to handle cytoplasmic dopamine may be a critical factor underlying t...
Preclinical efficacy of continuous delivery of 3,4-dihydroxyphenylalanine (DOPA) with adeno-associated viral (AAV) vecto...
In Huntington's disease (HD), the mutant huntingtin protein is ubiquitously expressed. The disease was considered to be ...
Dopamine replacement for Parkinson's disease (PD) have seen three major iterations of improvements since the introductio...
The ability to make specific perturbations to biological molecules in a cell or organism is a central experimental strat...