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Article ; Online: Poly(2-oxazoline)-Based Polyplexes as a PEG-Free Plasmid DNA Delivery Platform.

Yamaleyeva, Dina N / Makita, Naoki / Hwang, Duhyeong / Haney, Matthew J / Jordan, Rainer / Kabanov, Alexander V

2023 Volume 23, Issue 11, Page(s) e2300177

Abstract: The present study expands the versatility of cationic poly(2-oxazoline) (POx) copolymers as a polyethylene glycol (PEG)-free platform for gene delivery to immune cells, such as monocytes and macrophages. Several block copolymers are developed by varying ... ...

Abstract	The present study expands the versatility of cationic poly(2-oxazoline) (POx) copolymers as a polyethylene glycol (PEG)-free platform for gene delivery to immune cells, such as monocytes and macrophages. Several block copolymers are developed by varying nonionic hydrophilic blocks (poly(2-methyl-2-oxazoline) (pMeOx) or poly(2-ethyl-2-oxazoline) (pEtOx), cationic blocks, and an optional hydrophobic block (poly(2-isopropyl-2-oxazoline) (iPrOx). The cationic blocks are produced by side chain modification of 2-methoxy-carboxyethyl-2-oxazoline (MestOx) block precursor with diethylenetriamine (DET) or tris(2-aminoethyl)amine (TREN). For the attachment of a targeting ligand, mannose, azide-alkyne cycloaddition click chemistry methods are employed. Of the two cationic side chains, polyplexes made with DET-containing copolymers transfect macrophages significantly better than those made with TREN-based copolymer. Likewise, nontargeted pEtOx-based diblock copolymer is more active in cell transfection than pMeOx-based copolymer. The triblock copolymer with hydrophobic block iPrOx performs poorly compared to the diblock copolymer which lacks this additional block. Surprisingly, attachment of a mannose ligand to either copolymer is inhibitory for transfection. Despite similarities in size and design, mannosylated polyplexes result in lower cell internalization compared to nonmannosylated polyplexes. Thus, PEG-free, nontargeted DET-, and pEtOx-based diblock copolymer outperforms other studied structures in the transfection of macrophages and displays transfection levels comparable to GeneJuice, a commercial nonlipid transfection reagent.
MeSH term(s)	Polyethylene Glycols/chemistry ; Ligands ; Mannose ; Plasmids/genetics ; Polymers/chemistry ; DNA/chemistry ; Transfection
Chemical Substances	Polyethylene Glycols (3WJQ0SDW1A) ; poly(2-oxazoline) ; Ligands ; Mannose (PHA4727WTP) ; Polymers ; DNA (9007-49-2)
Language	English
Publishing date	2023-07-26
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2039130-4
ISSN	1616-5195 ; 1616-5187
ISSN (online)	1616-5195
ISSN	1616-5187
DOI	10.1002/mabi.202300177
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Article ; Online: The endocannabinoid system as a putative target for the development of novel drugs for the treatment of psychiatric illnesses.

Hill, Matthew N / Haney, Margaret / Hillard, Cecilia J / Karhson, Debra S / Vecchiarelli, Haley A

Psychological medicine

2023 Volume 53, Issue 15, Page(s) 7006–7024

Abstract: Cannabis is well established to impact affective states, emotion and perceptual processing, primarily through its interactions with the endocannabinoid system. While cannabis use is quite prevalent in many individuals afflicted with psychiatric illnesses, ...

Abstract	Cannabis is well established to impact affective states, emotion and perceptual processing, primarily through its interactions with the endocannabinoid system. While cannabis use is quite prevalent in many individuals afflicted with psychiatric illnesses, there is considerable controversy as to whether cannabis may worsen these conditions or provide some form of therapeutic benefit. The development of pharmacological agents which interact with components of the endocannabinoid system in more localized and discrete ways then via phytocannabinoids found in cannabis, has allowed the investigation if direct targeting of the endocannabinoid system itself may represent a novel approach to treat psychiatric illness without the potential untoward side effects associated with cannabis. Herein we review the current body of literature regarding the various pharmacological tools that have been developed to target the endocannabinoid system, their impact in preclinical models of psychiatric illness and the recent data emerging of their utilization in clinical trials for psychiatric illnesses, with a specific focus on substance use disorders, trauma-related disorders, and autism. We highlight several candidate drugs which target endocannabinoid function, particularly inhibitors of endocannabinoid metabolism or modulators of cannabinoid receptor signaling, which have emerged as potential candidates for the treatment of psychiatric conditions, particularly substance use disorder, anxiety and trauma-related disorders and autism spectrum disorders. Although there needs to be ongoing clinical work to establish the potential utility of endocannabinoid-based drugs for the treatment of psychiatric illnesses, the current data available is quite promising and shows indications of several potential candidate diseases which may benefit from this approach.
MeSH term(s)	Humans ; Endocannabinoids ; Mental Disorders/drug therapy ; Anxiety ; Anxiety Disorders ; Cannabis ; Cannabinoid Receptor Agonists ; Hallucinogens
Chemical Substances	Endocannabinoids ; Cannabinoid Receptor Agonists ; Hallucinogens
Language	English
Publishing date	2023-09-06
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	217420-0
ISSN	1469-8978 ; 0033-2917
ISSN (online)	1469-8978
ISSN	0033-2917
DOI	10.1017/S0033291723002465
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Article ; Online: Urinary Outcomes After Magnetic Resonance Imaging-Guided Whole-Gland Transurethral Ultrasound Ablation for Prostate Cancer: Comparison of Suprapubic Tube to Indwelling Urethral Catheter.

Rabinowitz, Matthew J / Haney, Nora M / Myers, Amanda A / Dora, Chandler D / Pavlovich, Christian P

Journal of endourology

2022 Volume 37, Issue 1, Page(s) 1–7

Abstract: Background: ...

Abstract	Background:
MeSH term(s)	Aged ; Humans ; Male ; Magnetic Resonance Imaging/adverse effects ; Prostatic Neoplasms/diagnostic imaging ; Prostatic Neoplasms/surgery ; Prostatic Neoplasms/complications ; Retrospective Studies ; Urinary Bladder/pathology ; Urinary Catheterization/adverse effects ; Urinary Catheters/adverse effects ; Urinary Incontinence/etiology
Language	English
Publishing date	2022-09-26
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	356931-7
ISSN	1557-900X ; 0892-7790
ISSN (online)	1557-900X
ISSN	0892-7790
DOI	10.1089/end.2022.0214
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Article: Y-Chromosome Microdeletions: A Review of Prevalence, Screening, and Clinical Considerations.

Rabinowitz, Matthew J / Huffman, Phillip J / Haney, Nora M / Kohn, Taylor P

The application of clinical genetics

2021 Volume 14, Page(s) 51–59

Abstract: Deletions within the male-specific region of the Y-chromosome, known as Y-Chromosome Microdeletions (YCMs), are present in as many as 5% and 10% of severe oligospermic and azoospermic men, respectively. These microdeletions are distinguished by which ... ...

Abstract	Deletions within the male-specific region of the Y-chromosome, known as Y-Chromosome Microdeletions (YCMs), are present in as many as 5% and 10% of severe oligospermic and azoospermic men, respectively. These microdeletions are distinguished by which segment of the Y chromosome is absent, identified as AZFa (the most proximal segment), AZFb (middle), and AZFc (distal). The reported prevalence of YCMs within the world's populations of infertile men displays vast heterogeneity, ranging from less than 2% to over 24% based on region and ethnicity. AZFc is the most commonly identified YCM, and its phenotypic presentation provides for the highest chance for fertility through artificial reproductive techniques. Conversely, deletions identified in the subregions of AZFa, AZFb, or any combination of regions containing these segments, are associated with low probabilities of achieving pregnancy. A putative mechanism explaining this discrepancy lies within the expression of autosomal, DAZ-like genes which could serve to "rescue" wild type AZFc gene expression and hence spermatogenesis. Nevertheless, recent reports challenge this dogma and stress the importance of further analysis when an AZFb deletion is detected. The screening thresholds to determine which oligospermic and azoospermic men are tested for potential YCMs has been recently contested. More recent literature supports lowering the threshold from 5 million sperm/mL of ejaculate to 1 million/mL as the frequency of YCMs in men with sperm concentrations between 1 and 5 million sperm/mL is very low (~0.8%). As such, subsequent guidelines should recommend a lower screening threshold. While YCMs are extremely common globally, the understanding of their clinical significance in the field remains scattered and without consensus. Furthermore, very little is currently known about partial deletions within the AZFc region, such as b1/b3, b2/b3, and gr/gr. Hence, this review aimed to summarize and discuss modern trends in the epidemiology, screening guidelines, and clinical considerations pertaining to YCMs.
Language	English
Publishing date	2021-02-12
Publishing country	New Zealand
Document type	Journal Article ; Review
ISSN	1178-704X
ISSN	1178-704X
DOI	10.2147/TACG.S267421
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Article ; Online: A Specific Earthquake Processing Workflow for Studying Long‐Lived, Explosive Volcanic Eruptions With Application to the 2008 Okmok Volcano, Alaska, Eruption

Garza‐Girón, Ricardo / Brodsky, Emily E. / Spica, Zack J. / Haney, Matthew M. / Webley, Peter W.

Journal of Geophysical Research: Solid Earth. 2023 May, v. 128, no. 5 p.e2022JB025882-

2023

Abstract: By providing unrivaled resolution in both time and space, volcano seismicity helps to chronicle and interpret eruptions. Standard earthquake detection methods are often insufficient as the eruption itself produces continuous seismic waves that obscure ... ...

Abstract	By providing unrivaled resolution in both time and space, volcano seismicity helps to chronicle and interpret eruptions. Standard earthquake detection methods are often insufficient as the eruption itself produces continuous seismic waves that obscure earthquake signals. We address this problem by developing an earthquake processing workflow specific to a high‐noise volcanic environment and applying it to the explosive 2008 Okmok Volcano eruption. This process includes applying single‐channel template matching combined with machine‐learning and fingerprint‐based techniques to expand the existing earthquake catalog of the eruption. We detected an order of magnitude more earthquakes, then located, relocated, determined locally calibrated magnitudes, and classified the events in the enhanced catalog. This new high‐resolution earthquake catalog increases the number of observations by about a factor of 10 and enables the detailed spatiotemporal seismic analysis during a large eruption.
Keywords	artificial intelligence ; earthquakes ; geophysics ; research ; Alaska
Language	English
Dates of publication	2023-05
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ISSN	2169-9313
DOI	10.1029/2022JB025882
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Extracellular Vesicles as Drug Carriers for Enzyme Replacement Therapy to Treat CLN2 Batten Disease: Optimization of Drug Administration Routes.

Haney, Matthew J / Zhao, Yuling / Jin, Yeon S / Batrakova, Elena V

Cells

2020 Volume 9, Issue 5

Abstract: CLN2 Batten disease (BD) is one of a broad class of lysosomal storage disorders that is characterized by the deficiency of lysosomal enzyme, TPP1, resulting in a build-up of toxic intracellular storage material in all organs and subsequent damage. A ... ...

Abstract	CLN2 Batten disease (BD) is one of a broad class of lysosomal storage disorders that is characterized by the deficiency of lysosomal enzyme, TPP1, resulting in a build-up of toxic intracellular storage material in all organs and subsequent damage. A major challenge for BD therapeutics is delivery of enzymatically active TPP1 to the brain to attenuate progressive loss of neurological functions. To accomplish this daunting task, we propose the harnessing of naturally occurring nanoparticles, extracellular vesicles (EVs). Herein, we incorporated TPP1 into EVs released by immune cells, macrophages, and examined biodistribution and therapeutic efficacy of EV-TPP1 in BD mouse model, using various routes of administration. Administration through intrathecal and intranasal routes resulted in high TPP1 accumulation in the brain, decreased neurodegeneration and neuroinflammation, and reduced aggregation of lysosomal storage material in BD mouse model, CLN2 knock-out mice. Parenteral intravenous and intraperitoneal administrations led to TPP1 delivery to peripheral organs: liver, kidney, spleen, and lungs. A combination of intrathecal and intraperitoneal EV-TPP1 injections significantly prolonged lifespan in BD mice. Overall, the optimization of treatment strategies is crucial for successful applications of EVs-based therapeutics for BD.
MeSH term(s)	Aminopeptidases/deficiency ; Aminopeptidases/metabolism ; Animals ; Brain/metabolism ; Brain/pathology ; Cells, Cultured ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/deficiency ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/metabolism ; Drug Administration Routes ; Drug Carriers/chemistry ; Enzyme Replacement Therapy ; Extracellular Vesicles/chemistry ; Humans ; Luminescent Measurements ; Mice, Inbred C57BL ; Mice, Knockout ; Neuronal Ceroid-Lipofuscinoses/therapy ; Neurons/metabolism ; Serine Proteases/deficiency ; Serine Proteases/metabolism ; Tissue Distribution ; Treatment Outcome ; Tripeptidyl-Peptidase 1
Chemical Substances	Drug Carriers ; Tpp1 protein, mouse ; Tripeptidyl-Peptidase 1 ; Serine Proteases (EC 3.4.-) ; Aminopeptidases (EC 3.4.11.-) ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases (EC 3.4.14.-) ; TPP1 protein, human (EC 3.4.14.9)
Language	English
Publishing date	2020-05-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells9051273
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Article ; Online: Earthquakes Record Cycles of Opening and Closing in the Enhanced Seismic Catalog of the 2008 Okmok Volcano, Alaska, Eruption

Garza‐Girón, Ricardo / Brodsky, Emily E. / Spica, Zack J. / Haney, Matthew M. / Webley, Peter W.

Journal of Geophysical Research: Solid Earth. 2023 July, v. 128, no. 7 p.e2023JB026893-

2023

Abstract: Seismicity during explosive volcanic eruptions remains challenging to observe through the eruptive noise, leaving first‐order questions unanswered. How do earthquake rates change as eruptions progress, and what is their relationship to the opening and ... ...

Abstract	Seismicity during explosive volcanic eruptions remains challenging to observe through the eruptive noise, leaving first‐order questions unanswered. How do earthquake rates change as eruptions progress, and what is their relationship to the opening and closing of the eruptive vent? To address these questions for the Okmok Volcano 2008 explosive eruption, Volcano Explosivity Index 4, we utilized modern detection methods to enhance the existing earthquake catalog. Our enhanced catalog detected significantly more earthquakes than traditional methods. We located, relocated, determined magnitudes and classified all events within this catalog. Our analysis reveals distinct behaviors for long‐period (LP) and volcano‐tectonic (VT) earthquakes, providing insights into the opening and closing cycle. LP earthquakes occur as bursts beneath the eruptive vent and do not coincide in time with the plumes, indicating their relationship to an eruptive process that occurs at a high pressurization state, that is, partially closed conduit. In contrast, VT earthquakes maintain a steadier rate over a broader region, do not track the caldera deflation and have a larger b‐value during the eruption than before or after. The closing sequence is marked by a burst of LPs followed by small VTs south of the volcano. The opening sequence differs as only VTs extend to depth and migrate within minutes of the eruption onset. Our high‐resolution catalog offers valuable insights, demonstrating that volcanic conduits can transition between partially closed (clogged) and open (cracked) states during an eruption. Utilizing modern earthquake processing techniques enables clearer understanding of eruptions and holds promise for studying other volcanic events.
Keywords	deflation ; earthquakes ; geophysics ; research ; Alaska
Language	English
Dates of publication	2023-07
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ISSN	2169-9313
DOI	10.1029/2023JB026893
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Extracellular Vesicles Released by Genetically Modified Macrophages Activate Autophagy and Produce Potent Neuroprotection in Mouse Model of Lysosomal Storage Disorder, Batten Disease.

El-Hage, Nazira / Haney, Matthew J / Zhao, Yuling / Rodriguez, Myosotys / Wu, Zhanhong / Liu, Mori / Swain, Carson J / Yuan, Hong / Batrakova, Elena V

Cells

2023 Volume 12, Issue 11

Abstract: Over the recent decades, the use of extracellular vesicles (EVs) has attracted considerable attention. Herein, we report the development of a novel EV-based drug delivery system for the transport of the lysosomal enzyme tripeptidyl peptidase-1 (TPP1) to ... ...

Abstract	Over the recent decades, the use of extracellular vesicles (EVs) has attracted considerable attention. Herein, we report the development of a novel EV-based drug delivery system for the transport of the lysosomal enzyme tripeptidyl peptidase-1 (TPP1) to treat Batten disease (BD). Endogenous loading of macrophage-derived EVs was achieved through transfection of parent cells with TPP1-encoding
MeSH term(s)	Mice ; Animals ; Neuronal Ceroid-Lipofuscinoses/metabolism ; Serine Proteases/genetics ; Aminopeptidases/genetics ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/metabolism ; Lipofuscin/metabolism ; Lipofuscin/therapeutic use ; Neuroprotection ; Tripeptidyl-Peptidase 1 ; Lysosomal Storage Diseases/metabolism ; Extracellular Vesicles/metabolism ; Lysosomes/metabolism ; Autophagy
Chemical Substances	Serine Proteases (EC 3.4.-) ; Aminopeptidases (EC 3.4.11.-) ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases (EC 3.4.14.-) ; Lipofuscin ; Tripeptidyl-Peptidase 1
Language	English
Publishing date	2023-05-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12111497
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Article ; Online: Using Extracellular Vesicles Released by GDNF-Transfected Macrophages for Therapy of Parkinson Disease.

Zhao, Yuling / Haney, Matthew J / Fallon, John K / Rodriguez, Myosotys / Swain, Carson J / Arzt, Camryn J / Smith, Philip C / Loop, Matthew Shane / Harrison, Emily B / El-Hage, Nazira / Batrakova, Elena V

Cells

2022 Volume 11, Issue 12

Abstract: Extracellular vesicles (EVs) are cell-derived nanoparticles that facilitate transport of proteins, lipids, and genetic material, playing important roles in intracellular communication. They have remarkable potential as non-toxic and non-immunogenic ... ...

Abstract	Extracellular vesicles (EVs) are cell-derived nanoparticles that facilitate transport of proteins, lipids, and genetic material, playing important roles in intracellular communication. They have remarkable potential as non-toxic and non-immunogenic nanocarriers for drug delivery to unreachable organs and tissues, in particular, the central nervous system (CNS). Herein, we developed a novel platform based on macrophage-derived EVs to treat Parkinson disease (PD). Specifically, we evaluated the therapeutic potential of EVs secreted by autologous macrophages that were transfected ex vivo to express glial-cell-line-derived neurotrophic factor (GDNF). EV-GDNF were collected from conditioned media of GDNF-transfected macrophages and characterized for GDNF content, size, charge, and expression of EV-specific proteins. The data revealed that, along with the encoded neurotrophic factor, EVs released by pre-transfected macrophages carry GDNF-encoding DNA. Four-month-old transgenic Parkin Q311(X)A mice were treated with EV-GDNF via intranasal administration, and the effect of this therapeutic intervention on locomotor functions was assessed over a year. Significant improvements in mobility, increases in neuronal survival, and decreases in neuroinflammation were found in PD mice treated with EV-GDNF. No offsite toxicity caused by EV-GDNF administration was detected. Overall, an EV-based approach can provide a versatile and potent therapeutic intervention for PD.
MeSH term(s)	Animals ; Central Nervous System ; Extracellular Vesicles/metabolism ; Glial Cell Line-Derived Neurotrophic Factor/genetics ; Glial Cell Line-Derived Neurotrophic Factor/metabolism ; Macrophages/metabolism ; Mice ; Parkinson Disease/genetics ; Parkinson Disease/metabolism ; Parkinson Disease/therapy
Chemical Substances	Glial Cell Line-Derived Neurotrophic Factor
Language	English
Publishing date	2022-06-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11121933
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Article ; Online: Corrigendum to "GDNF-expressing macrophages restore motor functions at a severe late-stage and produce long-term neuroprotective effects at an early-stage of Parkinson's disease in transgenic Parkin Q311X(A) mice", [J Control Release, 315 (2019) 139-149].

Zhao, Yuling / Haney, Matthew J / Jin, Yeon S / Uvarov, Olga / Vinod, Natasha / Lee, Yueh Z / Langworthy, Benjamin / Fine, Jason P / Rodriguez, Myosotys / El-Hage, Nazira / Kabanov, Alexander V / Batrakova, Elena V

Journal of controlled release : official journal of the Controlled Release Society

2022 Volume 343, Page(s) 813–814

Language	English
Publishing date	2022-01-25
Publishing country	Netherlands
Document type	Published Erratum
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2022.01.007
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