Classification of Schizophrenia, Bipolar Disorder and Major Depressive Disorder with Comorbid Traits and Deep Learning Algorithms.

Recent GWASs have demonstrated that comorbid disorders share genetic liabilities. But whether and how these shared liabilities can be used for the classification and differentiation of comorbid disorders remains unclear. In this study, we use polygenic risk scores (PRSs) estimated from 42 comorbid traits and the deep neural networks (DNN) architecture to classify and differentiate schizophrenia (SCZ), bipolar disorder (BIP) and major depressive disorder (MDD).

Methods for Retrovirus-Mediated Gene Transfer to CD34(+) Enriched Cells.

Hematopoietic stem cells (HSC) provide for contmuous replenishment of the entire immune and hematopoietic systems, and also replenish themselves in a process termed self-renewal (1).The HSCs can be enriched from hematopoietic tissues using MAbs that bind to the CD34 antigen, a universally recognized marker for hematopoietic progenitors (2-4).Enriched HSC populations are being widely investigated for use in transplantation and gene therapy because they appear to provide rapid hematopoietic reconstitution in myeloablated patients (5-11), and they offer good targets for gene transfer (12-17).

Human dendritic cells genetically engineered to express high levels of the human epithelial tumor antigen mucin (MUC-1).

We have achieved stable high-level expression of a human tumor antigen, epithelial cell mucin (MUC-1), on human dendritic cells (DCs) by retroviral transduction of CD34+ progenitor cells and their subsequent cytokine-induced differentiation into DCs. The process of retroviral transduction did not alter the growth or differentiation of DCs from CD34+ progenitor cells. Immunofluorescence and electron microscopy studies revealed that the expression of mucin was limited to the body of the DCs and was excluded from the cytoplasmic veils of the DCs.

A combination of CD34 selection and complement-mediated immunopurging (anti-CD15 monoclonal antibody) eliminates tumor cells while sparing normal progenitor cells.

Autologous bone marrow transplantation (ABMT) for acute myeloid leukemia (AML) in first complete remission (CR) results in a prolonged disease-free survival (DFS) of 34%-57%. Relapse of the underlying disease is the major cause for failure of ABMT. Relapse can result fom tumor cells either surviving in the patient or reinfused in the autograft.

Cytokine mobilization of peripheral blood stem cells in patients with Gaucher disease with a view to gene therapy.

As clinical trials for gene therapy in Gaucher disease (GD) begin, questions regarding the biology of the hematopoietic stem cell in this disease remain unanswered. This study demonstrates the ability to mobilize and collect CD34+ cells in three patients with the disorder. Our RAC/FDA-approved clinical trial utilizes mobilized peripheral blood stem cells (PBSC) as the target cells for gene transfer.

Efficient retroviral mediated transfer of the glucocerebrosidase gene in CD34+ enriched umbilical cord blood human hematopoietic progenitors.

Obtaining efficient transfer of a normal gene and its sustained expression in self-renewing hematopoietic stem cell populations is a central concern for gene therapy initiatives. Potentially, 10(8) to 10(9) CD34+ enriched cells per patient will be required for transduction and subsequent reimplantation. These studies present an efficient method for the transduction of human CD34+ cells that can be used in a clinical study of gene transfer.

Long-term expression of the glucocerebrosidase gene in mouse and human hematopoietic progenitors.

Gaucher disease (GD), one of the most common inherited metabolic disorders, is an excellent candidate for gene therapy using hematopoietic stem cells as targets. Animal models have demonstrated the feasibility of introducing the human glucocerebrosidase (GC) gene into hematopoietic progenitors with long term expression using a variety of retroviral vectors. We have previously demonstrated the expression and integration of the human GC gene in mouse hematopoietic progenitors and their progeny 4-8 months post transplant in primary recipients using the retroviral vector MFG-GC.

Centrifugal enhancement of retroviral mediated gene transfer.

Centrifugation has been used for many years to enhance infection of cultured cells with a variety of different types of viruses, but it has only recently been demonstrated to be effective for retroviruses (Ho et al. (1993) J. Leukocyte Biol.

A unique population of CD34+ cells in cord blood.

Human umbilical cord blood (CB) is a rich source of hematopoietic stem cells for both research and stem cell transplantation. In clinical studies, it appears that recovery from myeloablative therapy using CB requires significantly fewer cells than a typical allogeneic marrow transplant. This suggests that CB may be enriched for early hematopoietic progenitors.

Transduction of mobilized peripheral blood CD34+ cells with the glucocerebrosidase cDNA.

Gaucher disease (GD), the most common human lysosomal storage disorder, results from a genetic deficiency of the enzyme glucocerebrosidase (GC). The cloning of human GC cDNA, the benefits of allogeneic bone marrow transplantation and the success of enzyme replacement therapy support the feasibility of gene therapy as an approach to a cure for GD. We report the transfer of the GC gene to mobilized human peripheral blood (PB) CD34+ cells obtained from patients primed with granulocyte colony-stimulating factor and/or chemotherapy.

Transduction of CD34+ enriched cord blood and Gaucher bone marrow cells by a retroviral vector carrying the glucocerebrosidase gene.

One promising strategy for gene therapy of Gaucher disease involves ex vivo retroviral transduction of autologous hematopoietic stem cells. Studies in small animals have demonstrated that this approach provides a life-long supply of the glucocerebrosidase (GC) enzyme. Human application has developed to the stage of a clinical trial.