University of California

Csl Behring Gene Therapy, Inc.

Csl Gene Therapy Pty Ltd.

Calimmune, Inc.

Calimmune Australia Pty Ltd

Ming Yan

Yunfeng Lu

Geoffrey Phillip Symonds

Jeffrey S Bartlett

Zhen Gu

Yi Tang

Irvin S Y Chen

Cheng Ji

Min Liang

Anuradha Biswas

Guoping Fan

Jing Wen

Masakazu Kamata

Yang Liu

Otto O Yang

Chi-Lin Lee

Louis Randall Breton

Jeffrey Ahlers

Christopher Walter Alma

Gene-Errol Eugenio Ringpis

Irvin Sy Chen

Juanjuan Du

Irvin SY Chen

The present disclosure provides expression vectors comprising at least two nucleic acid sequences, namely a nucleic acid sequence encoding an anti-HPRT RNAi, and a nucleic acid sequence encoding a gamma globin gene. In some embodiments, the viral vector is a self-inactivating lentiviral vector. In some embodiments, the gamma-globin gene is used to genetically correct sickle cell disease or &#x3b2;-thalassemia or to reduce symptoms thereof.

Compositions and methods for treating beta-hemoglobinopathies

A method for intracellular delivery of single proteins or other cargo molecules by encapsulation within nanocapsules formed by interfacial polymerization of one or more types of monomers and selected protease cleavable cross-linkers is provided. The thin positively charged capsules are readily brought into the cytosol of target cells by endocytosis. The capsules are degraded by the action of endogenous proteases or co-delivered proteases on the cross-linkers releasing the functional cargo unaltered. The cross-linkers can be adapted to be cleavable by specific enzymes selected from available intracellular enzymes within the target cell or co-delivered or self-cleaving when the cargo itself is a protease. The nanocapsules produced by the methods have been shown to have long-term stability, high cell penetration capability, low toxicity and efficient protease-modulated specific degradability without affecting cargo protein function.

Protease assisted native-protein delivery approach (PANDA)

The disclosed methods are generally directed to preventing, treating, suppressing, controlling or otherwise mitigating side effects of T-cell therapy, the T-cell therapy designed to accelerate immune reconstitution, induce a GVM effect, and/or target tumor cells.

Modulatable switch for selection of donor modified cells

Novel siRNA and shRNA nanocapsules and delivery methods are disclosed herein. These siRNA and shRNA nanocapsules and delivery methods are highly robust and effective. This invention provides a platform for RNAi delivery with low toxicity and long intracellular half-life for practical therapeutic applications.

RNAi molecule delivery platform based on single-siRNA and shRNA nanocapsules

The invention provides novel methods, materials and systems that can be used to generate viral vectors having altered tissue and cell targeting abilities. In illustrative embodiments of the invention, the specificity of lentiviral vectors was modulated by a thin polymer shell that synthesized and coupled to the viral envelope in situ. The polymer shell can confers such vectors with new targeting ability via agents such as cyclic RGD (cRGD) peptides that are coupled to the polymer shell. These polymer encapsulated viral vectors exhibit a number of highly desirable characteristics including a higher thermal stability, resistance to serum inactivation in vivo, and an ability to infect dividing and non-dividing cells with high efficiencies.

Viral vector nanocapsule for targeting gene therapy and its preparation

Provided are nanocomplexes having at least two different enzymes and a polymeric network anchored to at least one of the enzymes. In some embodiments, the activities of the enzymes catalyze a cascade reaction.

Multiple-enzyme nanocomplexes

A protein nanocapsule having a single-protein core and a thin polymer shell anchored covalently to the protein core.

Single protein nanocapsules for protein delivery with long-term effect

Methods for protease assisted protein delivery

Growing community of inventors

Los Angeles, CA, United States of America

Ming Yan