Boris Kantor

Journal article Neurotherapeutics · August 18, 2026 Alpha-synuclein (SNCA) overexpression is implicated in Parkinson's disease (PD) pathogenesis, making SNCA downregulation a promising therapeutic strategy. We developed a SNCA-targeted transcriptional repression therapy using an all-in-one lentiviral vector ... Full text Link to item Cite

Cell-specific DNA methylation in human alpha and beta cells regulates gene expression in type 2 diabetes.

Journal article Nat Metab · April 2026 Epigenome-wide studies of pancreatic islets provide valuable insights into type 2 diabetes (T2D) but lack methylomes from individual cell types. Here we show changes to alpha and beta cell-specific methylomes and transcriptomes from people with or without ... Full text Link to item Cite

CRISPR-Cas editing technologies for viral-mediated gene therapies of human diseases: Mechanisms, progress, and challenges.

Journal article Mol Ther Nucleic Acids · March 12, 2026 The gene therapy landscape has evolved substantially in recent years, beginning with the approval of the first adeno-associated virus-based gene therapy, Luxterna, in 2017. Since then, the US FDA has approved nearly 30 new viral gene therapy programs, with ... Full text Link to item Cite

Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative disease.

Journal article Mol Ther Nucleic Acids · September 9, 2025 Recent advances in gene-editing technologies offer new opportunities for drug development to treat unmet medical needs in central nervous system (CNS) disorders including neurogenerative diseases of the aging brain. The adeno-associated virus (AAV) is a pr ... Full text Link to item Cite

The therapeutic implications of all-in-one AAV-delivered epigenome-editing platform in neurodegenerative disorders.

Journal article Nat Commun · August 23, 2024 Safely and efficiently controlling gene expression is a long-standing goal of biomedical research, and CRISPR/Cas system can be harnessed to create powerful tools for epigenetic editing. Adeno-associated-viruses (AAVs) represent the delivery vehicle of cho ... Full text Link to item Cite

All-in-one AAV-delivered epigenome-editing platform: proof-of-concept and therapeutic implications for neurodegenerative disorders.

Journal article bioRxiv · May 19, 2024 Safely and efficiently controlling gene expression is a long-standing goal of biomedical research, and the recently discovered bacterial CRISPR/Cas system can be harnessed to create powerful tools for epigenetic editing. Current state-of-the-art systems co ... Full text Link to item Cite

Neuronal-type-specific epigenome editing to decrease SNCA expression: Implications for precision medicine in synucleinopathies.

Journal article Mol Ther Nucleic Acids · March 12, 2024 Overexpression of SNCA has been implicated in the pathogenesis of synucleinopathies, particularly Parkinson's disease (PD) and dementia with Lewy bodies (DLB). While PD and DLB share some clinical and pathological similarities, each disease presents distin ... Full text Link to item Cite

Therapeutic modulation of gene expression in the disease state: Treatment strategies and approaches for the development of next-generation of the epigenetic drugs.

Journal article Front Bioeng Biotechnol · 2022 Epigenetic dysregulation is an important determinant of many pathological conditions and diseases. Designer molecules that can specifically target endogenous DNA sequences provide a means to therapeutically modulate gene function. The prokaryote-derived CR ... Full text Link to item Cite

Lentiviral Vectors for Delivery of Gene-Editing Systems Based on CRISPR/Cas: Current State and Perspectives.

Journal article Viruses · July 1, 2021 CRISPR/Cas technology has revolutionized the fields of the genome- and epigenome-editing by supplying unparalleled control over genomic sequences and expression. Lentiviral vector (LV) systems are one of the main delivery vehicles for the CRISPR/Cas system ... Full text Link to item Cite

Adeno-Associated Virus-Mediated Gene Therapy in the Mashlool, Atp1a3Mashl/+, Mouse Model of Alternating Hemiplegia of Childhood.

Journal article Hum Gene Ther · April 2021 Alternating Hemiplegia of Childhood (AHC) is a devastating autosomal dominant disorder caused by ATP1A3 mutations, resulting in severe hemiplegia and dystonia spells, ataxia, debilitating disabilities, and premature death. Here, we determine the effects of ... Full text Link to item Cite

The Path to Progress Preclinical Studies of Age-Related Neurodegenerative Diseases: A Perspective on Rodent and hiPSC-Derived Models.

Journal article Mol Ther · March 3, 2021 Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most prevalent age-related neurodegenerative diseases, and currently no effective clinical treatments exist for either, despite decades of clinical trials. The failure to translate preclinic ... Full text Link to item Cite

APOE: The New Frontier in the Development of a Therapeutic Target towards Precision Medicine in Late-Onset Alzheimer's.

Journal article Int J Mol Sci · January 27, 2021 Alzheimer's disease (AD) has a critical unmet medical need. The consensus around the amyloid cascade hypothesis has been guiding pre-clinical and clinical research to focus mainly on targeting beta-amyloid for treating AD. Nevertheless, the vast majority o ... Full text Link to item Cite

Cell-Type Specific Changes in DNA Methylation of SNCA Intron 1 in Synucleinopathy Brains.

Journal article Front Neurosci · 2021 Parkinson's disease (PD) and dementia with Lewy body (DLB) are the most common synucleinopathies. SNCA gene is a major genetic risk factor for these diseases group, and dysregulation of its expression has been implicated in the genetic etiologies of severa ... Full text Link to item Cite

An Improved Protocol for the Production of Lentiviral Vectors.

Journal article STAR Protoc · December 18, 2020 Lentiviral vectors are an ideal gene-delivery system for large gene-editing tools, such as the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 system, due to their high packaging capacity and broad tropism. Here, we present a calcium ... Full text Link to item Cite

The mechanistic role of alpha-synuclein in the nucleus: impaired nuclear function caused by familial Parkinson's disease SNCA mutations.

Journal article Hum Mol Genet · November 4, 2020 Alpha-synuclein SNCA has been implicated in the etiology of Parkinson's disease (PD); however, the normal function of alpha-synuclein protein and the pathway that mediates its pathogenic effect is yet to be discovered. We investigated the mechanistic role ... Full text Link to item Cite

Good problems to have? Policy and societal implications of a disease-modifying therapy for presymptomatic late-onset Alzheimer's disease.

Journal article Life Sci Soc Policy · October 12, 2020 In the United States alone, the prevalence of AD is expected to more than double from six million people in 2019 to nearly 14 million people in 2050. Meanwhile, the track record for developing treatments for AD has been marked by decades of failure. But re ... Full text Link to item Cite

Viral-Mediated Gene Replacement Therapy in the Developing Central Nervous System: Current Status and Future Directions.

Journal article Pediatr Neurol · September 2020 The past few years have witnessed rapid developments in viral-mediated gene replacement therapy for pediatric central nervous system neurogenetic disorders. Here, we provide pediatric neurologists with an up-to-date, comprehensive overview of these develop ... Full text Link to item Cite

Gene-Editing Technologies Paired With Viral Vectors for Translational Research Into Neurodegenerative Diseases.

Journal article Front Mol Neurosci · 2020 Diseases of the central nervous system (CNS) have historically been among the most difficult to treat using conventional pharmacological approaches. This is due to a confluence of factors, including the limited regenerative capacity and overall complexity ... Full text Link to item Cite

Lentiviral Vector Platform for the Efficient Delivery of Epigenome-editing Tools into Human Induced Pluripotent Stem Cell-derived Disease Models.

Journal article J Vis Exp · March 29, 2019 The use of hiPSC-derived cells represents a valuable approach to study human neurodegenerative diseases. Here, we describe an optimized protocol for the differentiation of hiPSCs derived from a patient with the triplication of the alpha-synuclein gene (SNC ... Full text Link to item Cite

Downregulation of SNCA Expression by Targeted Editing of DNA Methylation: A Potential Strategy for Precision Therapy in PD.

Journal article Mol Ther · November 7, 2018 Elevated levels of SNCA have been implicated in the pathogenesis of Parkinson's disease (PD), while normal physiological levels of SNCA are needed to maintain neuronal function. We ought to develop new therapeutic strategies targeting the regulation of SNC ... Full text Link to item Cite

A Protocol for the Production of Integrase-deficient Lentiviral Vectors for CRISPR/Cas9-mediated Gene Knockout in Dividing Cells.

Journal article J Vis Exp · December 12, 2017 Lentiviral vectors are an ideal choice for delivering gene-editing components to cells due to their capacity for stably transducing a broad range of cells and mediating high levels of gene expression. However, their ability to integrate into the host cell ... Full text Open Access Link to item Cite

Succination of Protein Disulfide Isomerase Links Mitochondrial Stress and Endoplasmic Reticulum Stress in the Adipocyte During Diabetes.

Journal article Antioxid Redox Signal · December 1, 2017 AIMS: Protein succination by fumarate increases in the adipose tissue of diabetic mice and in adipocytes matured in high glucose as a result of glucotoxicity-driven mitochondrial stress. The endoplasmic reticulum (ER) oxidoreductase protein disulfide isome ... Full text Link to item Cite

Integrase-Deficient Lentiviral Vector as an All-in-One Platform for Highly Efficient CRISPR/Cas9-Mediated Gene Editing.

Journal article Mol Ther Methods Clin Dev · June 16, 2017 The CRISPR/Cas9 systems have revolutionized the field of genome editing by providing unprecedented control over gene sequences and gene expression in many species, including humans. Lentiviral vectors (LVs) are one of the primary delivery platforms for the ... Full text Open Access Link to item Cite

Dominant-negative androgen receptor inhibition of intracrine androgen-dependent growth of castration-recurrent prostate cancer.

Journal article PLoS One · 2012 BACKGROUND: Prostate cancer (CaP) is the second leading cause of cancer death in American men. Androgen deprivation therapy is initially effective in CaP treatment, but CaP recurs despite castrate levels of circulating androgen. Continued expression of the ... Full text Link to item Cite

AAV exploits subcellular stress associated with inflammation, endoplasmic reticulum expansion, and misfolded proteins in models of cystic fibrosis.

Journal article PLoS Pathog · May 2011 Barriers to infection act at multiple levels to prevent viruses, bacteria, and parasites from commandeering host cells for their own purposes. An intriguing hypothesis is that if a cell experiences stress, such as that elicited by inflammation, endoplasmic ... Full text Link to item Cite

Notable reduction in illegitimate integration mediated by a PPT-deleted, nonintegrating lentiviral vector

Journal article Molecular Therapy · January 1, 2011 Nonintegrating lentiviral vectors present a means of reducing the risk of insertional mutagenesis in nondividing cells and enabling short-term expression of potentially hazardous gene products. However, residual, integrase-independent integration raises a ... Full text Cite

Proteasome inhibitors enhance gene delivery by AAV virus vectors expressing large genomes in hemophilia mouse and dog models: A strategy for broad clinical application

Journal article Molecular Therapy · January 1, 2010 Delivery of genes that are larger than the wild-type adeno-associated virus (AAV) 4,681 nucleotide genome is inefficient using AAV vectors. We previously demonstrated in vitro that concurrent proteasome inhibitor (PI) treatment improves transduction by AAV ... Full text Cite

Epigenetic activation of unintegrated HIV-1 genomes by gut-associated short chain fatty acids and its implications for HIV infection.

Journal article Proc Natl Acad Sci U S A · November 3, 2009 Integration of HIV-1 linear DNA into the host chromatin is an essential step in the viral life cycle. However, the majority of reverse-transcribed, nuclear-imported viral genomes remain episomal, either as linear or circular DNA. To date, these nonintegrat ... Full text Link to item Cite

A large U3 deletion causes increased in vivo expression from a nonintegrating lentiviral vector.

Journal article Mol Ther · December 2008 The feasibility of using nonintegrating lentiviral vectors has been demonstrated by recent studies showing their ability to maintain transgene expression both in vitro and in vivo. Furthermore, human immunodeficiency virus-1 (HIV-1) vectors packaged with a ... Full text Link to item Cite

DNA methylation in epigenetic control of gene expression.

Journal article Prog Mol Subcell Biol · 2005 Over three decades ago DNA methylation had been suggested to play a role in the regulation of gene expression. This chapter reviews the development of this field of research over the last three decades, from the time when this idea was proposed up until no ... Full text Link to item Cite

Establishing the epigenetic status of the Prader-Willi/Angelman imprinting center in the gametes and embryo.

Journal article Hum Mol Genet · November 15, 2004 The Prader-Willi/Angelman imprinted domain on human chromosome 15q11-q13 is regulated by an imprinting control center (IC) composed of a sequence around the SNRPN promoter (PWS-SRO) and a sequence located 35 kb upstream (AS-SRO). We have previously hypothe ... Full text Link to item Cite

Control elements within the PWS/AS imprinting box and their function in the imprinting process.

Journal article Hum Mol Genet · April 1, 2004 A cluster of imprinted genes on human chromosome 15q11-q13 (the PWS/AS domain) and its ortholog on mouse chromosome 7c is believed to be regulated by an imprinting control center. Although minideletions in this region in Angelman syndrome (AS) and Prader-W ... Full text Link to item Cite

Expression and localization of components of the histone deacetylases multiprotein repressory complexes in the mouse preimplantation embryo.

Journal article Gene Expr Patterns · December 2003 DNA methylation had been implicated in the assembly of multiprotein repressory complexes that affect chromatin architecture thereby rendering genes inactive. Proteins containing methyl binding domains (MBDs) are major components of these complexes. MBD3 is ... Full text Link to item Cite

Characterization of the human Snrpn minimal promoter and cis elements within it.

Journal article Gene · January 30, 2003 Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are caused by loss of gene function of the imprinted genes including Snrpn within a 2 Mb domain on chromosome 15q11-13. Based on microdeletions in PWS and AS patients, a 4.3 sequence around Snrpn promo ... Full text Link to item Cite

Tryptase activates the mitogen-activated protein kinase/activator protein-1 pathway in human peripheral blood eosinophils, causing cytokine production and release.

Journal article J Immunol · September 1, 2002 We have previously shown that mast cells enhance eosinophil survival and activation. In this study we further characterized mast cell activity toward eosinophils. Sonicate of both rat peritoneal mast cells and the human mast cell line 1 (HMC-1) induced a c ... Full text Link to item Cite

The mouse Snrpn minimal promoter and its human orthologue: activity and imprinting.

Journal article Genes Cells · November 2001 BACKGROUND: Microdeletions in chromosome 15q13-15 of Prader-Willi (PWS) and Angelman Syndrome (AS) patients suggested that SNRPN promoter/exon 1, together with a short sequence located approximately 35 kb upstream, constitute an imprinting control centre t ... Full text Link to item Cite