Delving into the Latest Updates on SJEFS-S19 with Synapse

Overview

Basic Info

Drug Type

Gene therapy

Synonyms-

Target

RPS19

Action

modulators

Mechanism

RPS19 modulators(ribosomal protein S19 modulators)

Therapeutic Areas

Congenital DisordersHemic and Lymphatic DiseasesOther Diseases

Active Indication

Anemia, Diamond-Blackfan

Inactive Indication-

Originator Organization

St. Jude Children's Research Hospital, Inc.

Active Organization

St. Jude Children's Research Hospital, Inc.

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Author: Mayberry, Kalin ; Gottschalk, Stephen ; Mayuranathan, Thiyagaraj ; Palmer, Lance E ; Zhang, Jingjing ; Yao, Yu ; Cheng, Yong ; Throm, Robert E ; Liu, Nana ; Ellis, Steven R ; Han, Lei ; Yan, Koon-Kiu ; Bhoopalan, Senthil Velan ; Yu, Jiyang ; Ju, Yan ; Weiss, Mitchell J ; Métais, Jean-Yves ; Zhou, Sheng ; Suryaprakash, Shruthi ; Yen, Jonathan S

Diamond-Blackfan anemia syndrome (DBAS) is an inherited bone marrow failure disorder caused by haploinsufficiency of ribosomal protein genes, most commonly RPS19. Limited access to patient hematopoietic stem and progenitor cells (HSPCs) is a major roadblock to developing novel therapies for DBAS. We developed a self-inactivating third-generation RPS19-encoding lentiviral vector (LV) called SJEFS-S19 for DBAS gene therapy. To facilitate LV design, optimize transduction, and assess potential therapeutic efficacy, we leveraged a human cellular model of DBAS based on heterozygous disruption of RPS19 in healthy donor CD34⁺ HSPCs. We show that SJEFS-S19 LV can rescue DBAS-associated defects in ribosomal RNA processing, erythropoiesis, and competitive bone marrow repopulation. Transduction of RPS19^+/- CD34⁺ HSPCs with SJEFS-S19 LV followed by xenotransplantation into immunodeficient mice generated a polyclonal HSPC population with normal multilineage differentiation and a diverse integration site profile resembling that of clinically proven LVs. Overall, these preclinical studies demonstrate the safety and efficacy of SJEFS-S19, a novel LV for future DBAS gene therapy.

100 Deals associated with SJEFS-S19

Login to view more data