University of California

California Institute of Technology

Irvin S Y Chen

David Baltimore

Xiao-Feng Qin

Dong Sung An

Carlos Lois-Caballe

Yunfeng Lu

Ming Yan

Min Liang

Jing Wen

Masakazu Kamata

Kouki Morizono

In one aspect, the invention provides methods and compositions for the expression of small RNA molecules within a cell using a retroviral vector (FIG.A). Small interfering RNA (siRNA) can be expressed using the methods of the invention within a cell. In a further aspect, the invention provides methods for producing siRNA encoding lentivirus where the siRNA activity may interfere with the lentiviral life cycle. In yet a further aspect, the invention provides methods for expression of a small RNA molecule within a cell, such as an siRNA capable of downregulating CCR5, wherein expression of the small RNA molecule is relatively non-cytotoxic to the cell. The invention also includes small RNA molecules, such as an siRNA capable of downregulating CCR5, that are relatively non-cytotoxic to cells.

Method for expression of small antiviral RNA molecules with reduced cytotoxicity within a cell

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

The present invention provides targeted lentiviral vectors that are psuedotyped with mutated Sindbis envelopes. For example, mutations in the Sindbis E2 protein are used to alter viral titer, specificity, specificity index, tropism, and susceptibility to host immune response. Typically, one or more of the E1, E2, or E3 proteins can be mutated at one or more amino acid positions. The psuedotyped, targeted lentiviral vectors of the invention are used to transduce heterologous genes into a cell and can be used for in vivo and ex vivo therapeutic applications, as well as for diagnostic and research tool applications.

Targeting pseudotyped retroviral vectors

In one aspect, the invention provides methods and compositions for the expression of small RNA molecules within a cell using a retroviral vector. The methods can be used to express double stranded RNA complexes. Small interfering RNA (siRNA) can be expressed using the methods of the invention within a cell, that interfere with a viral life cycle by down regulating either the viral genome, a viral genome transcript, or a host cell that. In another aspect the invention provides methods for treating patients having suffering from infection, particularly infection with HIV.

Method for expression of small antiviral RNA molecules within a cell

In one aspect, the invention provides methods and compositions for the expression of small RNA molecules within a cell using a retroviral vector (FIG.A). The methods can be used to express double stranded RNA complexes. Small interfering RNA (siRNA) can be expressed using the methods of the invention within a cell, that interfere with a viral life cycle by down regulating either the viral genome, a viral genome transcript, or a host cell that. In another aspect the invention provides methods for treating patients having suffering from infection, particularly infection with HIV. In a further aspect, the invention provides methods for producing siRNA encoding lentivirus where the siRNA activity may interfere with the lentiviral life cycle.

Growing community of inventors

Palos Verdes Estates, CA, United States of America

Irvin S Y Chen