Human Gene Therapy Research Institute

Newlink Genetics Corporation

Central Iowa Health System

Charles J Link, Jr

James N Higginbotham

Suming Wang

Tatiana Seregina

William J Ramsey

Rekha G Panchal

Mario Mautino

Nicholas N Vahanian

Won-Bin Young

John P Levy

Sheldon B Greer

Teresa Di Colandrea

Cherisa Meyer

W Jay Ramsey

Bradley J Powers

Sachet A Shukla

Won Bin Young

The invention includes a viral vector method and composition comprising transcomplementary replication incompetent viral vectors, preferably adenoviral vectors, which are cotransformed to a recipient cell. The two vectors complement each other and thus allow viral replication, in a synergistic combination which enhances both gene delivery and gene expression of genetic sequences contained within the vector.

Methods and compositions for efficient gene transfer using transcomplementary vectors

A method is described for the rapid identification and isolation of cells based on the presence or absence of an ectopically-expressed N-acetyllactosaminide 3-&#x3b1; Galactosyltransferase (&#x3b1;GT) enzyme for the production of &#x3b1;Galactosyl-(1,3)Galactosyl (&#x3b1;Gal) epitopes on the surface of &#x3b1;Gal-negative cells. These cells which are genetically modified to express the &#x3b1;GT enzyme and &#x3b1;Gal epitopes on glycosylated lipids and proteins of the cell surface are then labeled via an antibody composition which recognizes and binds the &#x3b1;Gal epitopes on the cell surface. Cells labeled with the anti-&#x3b1;Gal antibody can be isolated by sorting via fluorescence activated cell sorting (FACS), or by magnetic panning techniques. This method is suitable for the rapid positive or negative selection of &#x3b1;Gal-positive cells from within a population of &#x3b1;Gal-negative cells without the need to expose cells to antibiotics for any period of time. In addition, the specification provides a method for the production and purification of anti-&#x3b1;Gal antibodies from chicken egg yolk.

Selectable gene marker system based on expression of N-acetyllactosaminide 3-&#x3b1; galactosyltransferase

Novel synthetic suppressor tRNA have been provided which provide read-through of internal nonsense mutations, or which can site-specifically alter translation of transcribed sequences. Uses of the same are also provided in genetic engineering protocols including gene therapy treatment of diseases such as Xeroderma pigmentosum.

Human suppressor tRNA oligonucleotides and methods for use for same

The present invention relates generally to methods and compositions for the identification of differential protein expression patterns and concomitantly the active genetic regions that are directly or indirectly involved in different tissue types, disease states, or other cellular differences desirable for diagnosis or for targets for drug therapy.

Methods and compositions for elucidating relative protein expression levels in cells

The present invention describes an efficient retroviral or viral based method that allows easy and quick identification of gene transfer in living, transduced mammalian cells. Retroviral and viral vector producer cells were generated containing a gene for an improved humanized red-shifted, Green Fluorescent Protein (hRGFP) which increases the resulting fluorescence yield after excitation. This humanized, red-shifted GFP (hRGFP) gene was cloned into several vectors and transfected into various packaging cell lines to produce vibrant green fluorescence after excitation with blue light at 450-490 nm. These vectors represent a substantial advance over currently available gene transfer marking systems or wild-type GFP marker systems none of which have been stably transfected into cells.

Vehicles for stable transfer of green fluorescent protein gene and methods of use for same

Human suppressor tRNA oligonucleotides and methods of use for same

The present invention pertains to combination radio therapy of tumors and more specifically to pharmaceutical compositions, and methods of treatment by gene therapy designed to sensitize tumors in animals, notably humans, and render them more susceptible to radiation, thus significantly reducing the amount of radiation required to kill neoplastic cells while at the same time making the radiation far more tissue specific to the tumor site.

Radiation enhanced therapy for tumors expressing a gene for viral

Disclosed herein is the method for dramatically reducing cytotoxicity of viral vectors such as Herpes simplex viral while retaining gene expression. The method of the invention virtually eliminates the concern of possible recombination during virus propagation and contamination of wild-type virus and virus stock. The invention comprises use of photochemical crosslinking causing differential inactivation of viruses.

Differential inactivation of nucleic acids by chemical modification

A novel HSV mini viral vector is disclosed. The vector comprises HSV and EBV genes which allow it to remain in episomal state, to have very high transfection and infection, and to tolerate up to 140 kb of foreign DNA. Techniques and genetic constructs for producing the vectors, for constructing the vectors and transfection and infection to recipient cells are disclosed.

Growing community of inventors

Des Moines, IA, United States of America

Charles J Link, Jr