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Article: Molecular/genetic manipulation of extrinsic axon guidance factors for CNS repair and regeneration.

Curinga, Gabrielle / Smith, George M

2008 Volume 209, Issue 2, Page(s) 333–342

Abstract: During development, guidance molecules play a key role in the formation of complex circuits required for neural functions. With the cessation of development, this exuberant growth process slows and stabilizes, and inhibitory molecules expressed by glia ... ...

Abstract	During development, guidance molecules play a key role in the formation of complex circuits required for neural functions. With the cessation of development, this exuberant growth process slows and stabilizes, and inhibitory molecules expressed by glia prevent initial attempts for axonal regeneration. In this review, we discuss the expression patterns and relative contribution of several guidance molecules on the regenerative process. Injury to the immature CNS or species capable of regenerating exhibit a complete or partial recapitulation of their developmental guidance patterns, whereas similar injuries to adult mammals results in altered expression that acts to further hinder regeneration. Manipulations of guidance molecules after injury have been used to control detrimental effects of axon sprouting and target regenerating axons within the spinal cord.
MeSH term(s)	Animals ; Axons/physiology ; Central Nervous System/pathology ; Central Nervous System/physiopathology ; Humans ; Molecular Biology/methods ; Nerve Regeneration/genetics ; Wound Healing/genetics
Language	English
Publishing date	2008-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	207148-4
ISSN	1090-2430 ; 0014-4886
ISSN (online)	1090-2430
ISSN	0014-4886
DOI	10.1016/j.expneurol.2007.06.026
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Article: Mechanisms regulating interpretation of guidance cues during development, maturation, and following injury.

Curinga, Gabrielle / Snow, Diane M / Smith, George M

Reviews in the neurosciences

2008 Volume 19, Issue 4-5, Page(s) 213–226

Abstract: Guidance molecules are not inherently attractive or repulsive, but rather, are interpreted as such based on the context in which they are encountered. Thus, accurate wiring of the central nervous system is inextricably tied to the internal state of ... ...

Abstract	Guidance molecules are not inherently attractive or repulsive, but rather, are interpreted as such based on the context in which they are encountered. Thus, accurate wiring of the central nervous system is inextricably tied to the internal state of neurons and their local environment. To protect functional integrity, these carefully formed circuits are stabilized via a combination of neuronal and environmental changes during maturation and following injury. While necessary, such modifications create obstacles for reconstruction of damaged circuits. Here, we consider the effects of maturation and injury induced changes on the interpretation of guidance cues by regenerating neurons and the problems they pose for faithful reconstruction of functional circuits.
MeSH term(s)	Animals ; Cues ; Humans ; Nerve Regeneration/physiology ; Nerve Tissue Proteins/physiology ; Nervous System/cytology ; Nervous System/embryology ; Nervous System/growth & development ; Nervous System Diseases/physiopathology
Chemical Substances	Nerve Tissue Proteins
Language	English
Publishing date	2008-02-29
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	639035-3
ISSN	2191-0200 ; 0334-1763
ISSN (online)	2191-0200
ISSN	0334-1763
DOI	10.1515/revneuro.2008.19.4-5.213
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Article: Elevated extracellular calcium levels induce smooth muscle cell matrix mineralization in vitro.

Yang, Hsueh / Curinga, Gabrielle / Giachelli, Cecilia M

Kidney international

2004 Volume 66, Issue 6, Page(s) 2293–2299

Abstract: Background: Hyperphosphatemia, elevated calcium x phosphorus product (Ca x P), and calcium burden, major causes of vascular calcification, are correlated with increased cardiovascular morbidity and mortality in dialysis patients.: Methods: To address ...

Abstract	Background: Hyperphosphatemia, elevated calcium x phosphorus product (Ca x P), and calcium burden, major causes of vascular calcification, are correlated with increased cardiovascular morbidity and mortality in dialysis patients. Methods: To address the underlying mechanisms responsible for these findings, we have utilized an in vitro human smooth muscle cell (HSMC) model of vascular calcification. Previous studies using this system demonstrated enhanced calcification of HSMC cultures treated with phosphorus levels in the hyperphosphatemic range, and implicated a sodium-dependent phosphate cotransport-dependent mechanism in this effect. In the present study, we examine the effect of increasing calcium concentrations on HSMC calcification in vitro. Results: Increasing calcium to levels observed in hypercalcemic individuals increased mineralization of HSMC cultures under normal phosphorus conditions. Importantly, at these total calcium concentrations, ionized calcium levels increased from 1.2 mmol/L to 1.7 mmol/L, consistent with levels observed physiologically in normocalcemic and hypercalcemic individuals, respectively. Furthermore, increasing both calcium and phosphorus levels led to accelerated and increased mineralization in the cultures. Calcium-induced mineralization was dependent on the function of a sodium-dependent phosphate cotransporter, since it was inhibited by phosphonoformic acid (PFA). While elevated calcium did not affect short-term phosphorus transport kinetics, long-term elevated calcium treatment of HSMCs induced expression of the sodium-dependent phosphate cotransporter, Pit-1. Conclusion: These studies suggest that elevated calcium may stimulate HSMC mineralization by elevating Ca x P product and enhancing the sodium-dependent phosphate cotransporter-dependent mineralization pathway previously observed in HSMCs.
MeSH term(s)	Aorta/cytology ; Calcification, Physiologic/physiology ; Calcinosis/metabolism ; Calcium/metabolism ; Calcium/pharmacology ; Cells, Cultured ; Extracellular Matrix/metabolism ; Extracellular Space/metabolism ; Humans ; Hypercalcemia/metabolism ; In Vitro Techniques ; Muscle, Smooth, Vascular/cytology ; Muscle, Smooth, Vascular/drug effects ; Muscle, Smooth, Vascular/metabolism ; Phosphorus/metabolism ; Phosphorus/pharmacology ; Signal Transduction/physiology
Chemical Substances	Phosphorus (27YLU75U4W) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2004-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1111/j.1523-1755.2004.66015.x
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Article ; Online: Comparison of sensory neuron growth cone and filopodial responses to structurally diverse aggrecan variants, in vitro.

Beller, Justin A / Kulengowski, Brandon / Kobraei, Edward M / Curinga, Gabrielle / Calulot, Christopher M / Bahrami, Azita / Hering, Thomas M / Snow, Diane M

Experimental neurology

2013 Volume 247, Page(s) 143–157

Abstract: Following spinal cord injury, a regenerating neurite encounters a glial scar enriched in chondroitin sulfate proteoglycans (CSPGs), which presents a major barrier. There are two points at which a neurite makes contact with glial scar CSPGs: initially, ... ...

Abstract	Following spinal cord injury, a regenerating neurite encounters a glial scar enriched in chondroitin sulfate proteoglycans (CSPGs), which presents a major barrier. There are two points at which a neurite makes contact with glial scar CSPGs: initially, filopodia surrounding the growth cone extend and make contact with CSPGs, then the peripheral domain of the entire growth cone makes CSPG contact. Aggrecan is a CSPG commonly used to model the effect CSPGs have on elongating or regenerating neurites. In this study, we investigated filopodia and growth cone responses to contact with structurally diverse aggrecan variants using the common stripe assay. Using time-lapse imaging with 15-s intervals, we measured growth cone area, growth cone width, growth cone length, filopodia number, total filopodia length, and the length of the longest filopodia following contact with aggrecan. Responses were measured after both filopodia and growth cone contact with five different preparations of aggrecan: two forms of aggrecan derived from bovine articular cartilage (purified and prepared using different techniques), recombinant aggrecan lacking chondroitin sulfate side chains (produced in CHO-745 cells) and two additional recombinant aggrecan preparations with varying lengths of chondroitin sulfate side chains (produced in CHO-K1 and COS-7 cells). Responses in filopodia and growth cone behavior differed between the structurally diverse aggrecan variants. Mutant CHO-745 aggrecan (lacking chondroitin sulfate chains) permitted extensive growth across the PG stripe. Filopodia contact with the CHO-745 aggrecan caused a significant increase in growth cone width and filopodia length (112.7% ± 4.9 and 150.9% ± 7.2 respectively, p<0.05), and subsequently upon growth cone contact, growth cone width remained elevated along with a reduction in filopodia number (121.9% ± 4.2; 72.39% ± 6.4, p<0.05). COS-7 derived aggrecan inhibited neurite outgrowth following growth cone contact. Filopodia contact produced an increase in growth cone area and width (126.5% ± 8.1; 150.3% ± 13.31, p<0.001), and while these parameters returned to baseline upon growth cone contact, a reduction in filopodia number and length was observed (73.94% ± 5.8, 75.3% ± 6.2, p<0.05). CHO-K1 derived aggrecan inhibited neurite outgrowth following filopodia contact, and caused an increase in growth cone area and length (157.6% ± 6.2; 117.0% ± 2.8, p<0.001). Interestingly, the two bovine articular cartilage aggrecan preparations differed in their effects on neurite outgrowth. The proprietary aggrecan (BA I, Sigma-Aldrich) inhibited neurites at the point of growth cone contact, while our chemically purified aggrecan (BA II) inhibited neurite outgrowth at the point of filopodia contact. BA I caused a reduction in growth cone width following filopodia contact (91.7% ± 2.5, p<0.05). Upon growth cone contact, there was a further reduction in growth cone width and area (66.4% ± 2.2; 75.6% ± 2.9; p<0.05), as well as reductions in filopodia number, total length, and max length (75.9% ± 5.7, p<0.05; 68.8% ± 6.0; 69.6% ± 3.5, p<0.001). Upon filopodia contact, BA II caused a significant increase in growth cone area, and reductions in filopodia number and total filopodia length (115.9% ± 5.4, p<0.05; 72.5% ± 2.7; 77.7% ± 3.2, p<0.001). In addition, filopodia contact with BA I caused a significant reduction in growth cone velocity (38.6 nm/s ± 1.3 before contact, 17.1 nm/s ± 3.6 after contact). These data showed that neuron morphology and behavior are differentially dependent upon aggrecan structure. Furthermore, the behavioral changes associated with the approaching growth cone may be predictive of inhibition or growth.
MeSH term(s)	Aggrecans/metabolism ; Animals ; Cattle ; Cell Line, Transformed ; Cells, Cultured ; Chickens ; Chlorocebus aethiops ; Chondroitin Sulfates/chemistry ; Cricetulus ; Embryo, Mammalian ; Ganglia, Spinal/cytology ; Growth Cones/physiology ; Growth Cones/ultrastructure ; Microscopy, Confocal ; Pseudopodia/physiology ; Pseudopodia/ultrastructure ; Sensory Receptor Cells/cytology ; Time Factors ; Transfection
Chemical Substances	Aggrecans ; Chondroitin Sulfates (9007-28-7)
Language	English
Publishing date	2013-03-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	207148-4
ISSN	1090-2430 ; 0014-4886
ISSN (online)	1090-2430
ISSN	0014-4886
DOI	10.1016/j.expneurol.2013.02.012
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Article ; Online: Rapamycin relieves lentiviral vector transduction resistance in human and mouse hematopoietic stem cells.

Wang, Cathy X / Sather, Blythe D / Wang, Xuefeng / Adair, Jennifer / Khan, Iram / Singh, Swati / Lang, Shanshan / Adams, Amie / Curinga, Gabrielle / Kiem, Hans-Peter / Miao, Carol H / Rawlings, David J / Torbett, Bruce E

Blood

2014 Volume 124, Issue 6, Page(s) 913–923

Abstract: Transplantation of genetically modified hematopoietic stem cells (HSCs) is a promising therapeutic strategy for genetic diseases, HIV, and cancer. However, a barrier for clinical HSC gene therapy is the limited efficiency of gene delivery via lentiviral ... ...

Abstract	Transplantation of genetically modified hematopoietic stem cells (HSCs) is a promising therapeutic strategy for genetic diseases, HIV, and cancer. However, a barrier for clinical HSC gene therapy is the limited efficiency of gene delivery via lentiviral vectors (LVs) into HSCs. We show here that rapamycin, an allosteric inhibitor of the mammalian target of rapamycin complexes, facilitates highly efficient lentiviral transduction of mouse and human HSCs and dramatically enhances marking frequency in long-term engrafting cells in mice. Mechanistically, rapamycin enhanced postbinding endocytic events, leading to increased levels of LV cytoplasmic entry, reverse transcription, and genomic integration. Despite increasing LV copy number, rapamycin did not significantly alter LV integration site profile or chromosomal distribution in mouse HSCs. Rapamycin also enhanced in situ transduction of mouse HSCs via direct intraosseous infusion. Collectively, rapamycin strongly augments LV transduction of HSCs in vitro and in vivo and may prove useful for therapeutic gene delivery.
MeSH term(s)	Animals ; Genetic Vectors/drug effects ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/drug effects ; Hematopoietic Stem Cells/metabolism ; Hematopoietic Stem Cells/virology ; Heterografts ; Humans ; Lentivirus/drug effects ; Lentivirus/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, SCID ; Sirolimus/pharmacology ; TOR Serine-Threonine Kinases/antagonists & inhibitors ; TOR Serine-Threonine Kinases/metabolism ; Transduction, Genetic/methods ; Virus Internalization/drug effects
Chemical Substances	TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Sirolimus (W36ZG6FT64)
Language	English
Publishing date	2014-06-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2013-12-546218
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Article ; Online: Efficient modification of CCR5 in primary human hematopoietic cells using a megaTAL nuclease and AAV donor template.

Sather, Blythe D / Romano Ibarra, Guillermo S / Sommer, Karen / Curinga, Gabrielle / Hale, Malika / Khan, Iram F / Singh, Swati / Song, Yumei / Gwiazda, Kamila / Sahni, Jaya / Jarjour, Jordan / Astrakhan, Alexander / Wagner, Thor A / Scharenberg, Andrew M / Rawlings, David J

Science translational medicine

2015 Volume 7, Issue 307, Page(s) 307ra156

Abstract: Genetic mutations or engineered nucleases that disrupt the HIV co-receptor CCR5 block HIV infection of CD4(+) T cells. These findings have motivated the engineering of CCR5-specific nucleases for application as HIV therapies. The efficacy of this ... ...

Abstract	Genetic mutations or engineered nucleases that disrupt the HIV co-receptor CCR5 block HIV infection of CD4(+) T cells. These findings have motivated the engineering of CCR5-specific nucleases for application as HIV therapies. The efficacy of this approach relies on efficient biallelic disruption of CCR5, and the ability to efficiently target sequences that confer HIV resistance to the CCR5 locus has the potential to further improve clinical outcomes. We used RNA-based nuclease expression paired with adeno-associated virus (AAV)-mediated delivery of a CCR5-targeting donor template to achieve highly efficient targeted recombination in primary human T cells. This method consistently achieved 8 to 60% rates of homology-directed recombination into the CCR5 locus in T cells, with over 80% of cells modified with an MND-GFP expression cassette exhibiting biallelic modification. MND-GFP-modified T cells maintained a diverse repertoire and engrafted in immune-deficient mice as efficiently as unmodified cells. Using this method, we integrated sequences coding chimeric antigen receptors (CARs) into the CCR5 locus, and the resulting targeted CAR T cells exhibited antitumor or anti-HIV activity. Alternatively, we introduced the C46 HIV fusion inhibitor, generating T cell populations with high rates of biallelic CCR5 disruption paired with potential protection from HIV with CXCR4 co-receptor tropism. Finally, this protocol was applied to adult human mobilized CD34(+) cells, resulting in 15 to 20% homologous gene targeting. Our results demonstrate that high-efficiency targeted integration is feasible in primary human hematopoietic cells and highlight the potential of gene editing to engineer T cell products with myriad functional properties.
MeSH term(s)	Adult ; Antigens, CD34/metabolism ; CD3 Complex/metabolism ; Cells, Cultured ; DNA Repair ; Deoxyribonucleases/metabolism ; Dependovirus/metabolism ; Genetic Loci ; Genetic Therapy ; Green Fluorescent Proteins/metabolism ; Hematopoietic Stem Cells/metabolism ; Humans ; RNA Editing/genetics ; Receptors, Antigen, T-Cell/metabolism ; Receptors, CCR5/metabolism ; T-Lymphocytes/metabolism
Chemical Substances	Antigens, CD34 ; CD3 Complex ; Receptors, Antigen, T-Cell ; Receptors, CCR5 ; Green Fluorescent Proteins (147336-22-9) ; Deoxyribonucleases (EC 3.1.-)
Language	English
Publishing date	2015-09-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.aac5530
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Article: Mammalian-produced chondroitinase AC mitigates axon inhibition by chondroitin sulfate proteoglycans

Curinga, Gabrielle M / Snow, Diane M / Mashburn, Charles / Kohler, Katharina / Thobaben, Rebecca / Caggiano, Anthony O / Smith, George M

Journal of neurochemistry. 2007 July, v. 102, no. 1

2007

Abstract: Chondroitin sulfate proteoglycans (CSPGs) are up-regulated following spinal cord injury and are partly responsible for failed regeneration. Experimental paradigms in vivo that degrade chondroitin sulfate glycosaminoglycan chains with the bacterial enzyme, ...

Abstract	Chondroitin sulfate proteoglycans (CSPGs) are up-regulated following spinal cord injury and are partly responsible for failed regeneration. Experimental paradigms in vivo that degrade chondroitin sulfate glycosaminoglycan chains with the bacterial enzyme, chondroitinase, greatly enhance the ability of axons to regenerate through the glial scar. Unfortunately, enthusiasm for this treatment paradigm is diminished by the lack of a minimally invasive and sustained delivery method. To address these deficits, we have engineered a Tet-On adenoviral vector encoding chondroitinase AC and have characterized its enzymatic function in vitro. U373 human astrocytoma cells were transduced with adenovirus and subsequently induced with doxycycline to secrete enzymatically active chondroitinase as detected by western blot and kinetic analyses. Enzymatic activity demonstrated biological relevance in studies where neurite outgrowth into and across CSPG-adsorbed regions pre-treated with conditioned media from chondroitinase secreting astrocytes was significantly increased compared with untreated controls (p < 0.0001). We also measured important parameters of enzyme activity including: pH, temperature, and enzyme stability that are fundamental to harnessing the true therapeutic potential of this approach. The use of resident cells for continuous secretion of CSPG-degrading enzymes at the site of the glial scar promises to be of greater clinical relevance than contemporary methods.
Keywords	glycosaminoglycans ; sensory neurons
Language	English
Dates of publication	2007-07
Size	p. 275-288.
Publisher	Blackwell Publishing Ltd
Publishing place	Oxford, UK
Document type	Article
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/j.1471-4159.2007.04530.x
Database	NAL-Catalogue (AGRICOLA)

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Article: Mammalian-produced chondroitinase AC mitigates axon inhibition by chondroitin sulfate proteoglycans.

Curinga, Gabrielle M / Snow, Diane M / Mashburn, Charles / Kohler, Katharina / Thobaben, Rebecca / Caggiano, Anthony O / Smith, George M

Journal of neurochemistry

2007 Volume 102, Issue 1, Page(s) 275–288

Abstract	Chondroitin sulfate proteoglycans (CSPGs) are up-regulated following spinal cord injury and are partly responsible for failed regeneration. Experimental paradigms in vivo that degrade chondroitin sulfate glycosaminoglycan chains with the bacterial enzyme, chondroitinase, greatly enhance the ability of axons to regenerate through the glial scar. Unfortunately, enthusiasm for this treatment paradigm is diminished by the lack of a minimally invasive and sustained delivery method. To address these deficits, we have engineered a Tet-On adenoviral vector encoding chondroitinase AC and have characterized its enzymatic function in vitro. U373 human astrocytoma cells were transduced with adenovirus and subsequently induced with doxycycline to secrete enzymatically active chondroitinase as detected by western blot and kinetic analyses. Enzymatic activity demonstrated biological relevance in studies where neurite outgrowth into and across CSPG-adsorbed regions pre-treated with conditioned media from chondroitinase secreting astrocytes was significantly increased compared with untreated controls (p < 0.0001). We also measured important parameters of enzyme activity including: pH, temperature, and enzyme stability that are fundamental to harnessing the true therapeutic potential of this approach. The use of resident cells for continuous secretion of CSPG-degrading enzymes at the site of the glial scar promises to be of greater clinical relevance than contemporary methods.
MeSH term(s)	Adenoviridae/genetics ; Animals ; Axons/physiology ; Blotting, Western ; Cell Line, Tumor ; Cells, Cultured ; Chickens ; Chondroitin Lyases/chemistry ; Chondroitin Lyases/genetics ; Chondroitin Lyases/physiology ; Chondroitin Sulfates/antagonists & inhibitors ; Chondroitin Sulfates/pharmacology ; Cloning, Molecular ; Doxycycline/pharmacology ; Ganglia, Spinal/cytology ; Ganglia, Spinal/drug effects ; Humans ; Hydrogen-Ion Concentration ; Immunoprecipitation ; Nerve Regeneration/drug effects ; Neurons, Afferent/drug effects ; Proteoglycans/antagonists & inhibitors ; Proteoglycans/pharmacology ; Signal Transduction/drug effects ; Temperature
Chemical Substances	Proteoglycans ; Chondroitin Sulfates (9007-28-7) ; Chondroitin Lyases (EC 4.2.2.-) ; Doxycycline (N12000U13O)
Language	English
Publishing date	2007-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/j.1471-4159.2007.04530.x
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Article ; Online: Coupling endonucleases with DNA end-processing enzymes to drive gene disruption.

Certo, Michael T / Gwiazda, Kamila S / Kuhar, Ryan / Sather, Blythe / Curinga, Gabrielle / Mandt, Tyler / Brault, Michelle / Lambert, Abigail R / Baxter, Sarah K / Jacoby, Kyle / Ryu, Byoung Y / Kiem, Hans-Peter / Gouble, Agnes / Paques, Frederic / Rawlings, David J / Scharenberg, Andrew M

Nature methods

2012 Volume 9, Issue 10, Page(s) 973–975

Abstract: Targeted DNA double-strand breaks introduced by rare-cleaving designer endonucleases can be harnessed for gene disruption applications by engaging mutagenic nonhomologous end-joining DNA repair pathways. However, endonuclease-mediated DNA breaks are ... ...

Abstract	Targeted DNA double-strand breaks introduced by rare-cleaving designer endonucleases can be harnessed for gene disruption applications by engaging mutagenic nonhomologous end-joining DNA repair pathways. However, endonuclease-mediated DNA breaks are often subject to precise repair, which limits the efficiency of targeted genome editing. To address this issue, we coupled designer endonucleases to DNA end-processing enzymes to drive mutagenic break resolution, achieving up to 25-fold enhancements in gene disruption rates.
MeSH term(s)	Animals ; DNA Breaks, Double-Stranded ; DNA End-Joining Repair ; DNA Repair ; Endonucleases/physiology ; Exodeoxyribonucleases/physiology ; HEK293 Cells ; Humans ; Mice ; Phosphoproteins/physiology ; Receptors, CCR5/physiology
Chemical Substances	Phosphoproteins ; Receptors, CCR5 ; Endonucleases (EC 3.1.-) ; Exodeoxyribonucleases (EC 3.1.-) ; TREX2 protein, human (EC 3.1.16.-)
Language	English
Publishing date	2012-09-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2169522-2
ISSN	1548-7105 ; 1548-7091
ISSN (online)	1548-7105
ISSN	1548-7091
DOI	10.1038/nmeth.2177
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