107 results about "Retrovirus" patented technology

Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AV vectors, herpes viral vectors, and retroviral vectors) that encode OCT4; KLF4; SOX2; or any combination thereof that are useful, for example, in inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, or any combination thereof. Also provided herein are recombinant viruses (e.g., lentiviruses, alphaviruses, vaccinia viruses, adenoviruses, herpes viruses, retroviruses, or AAVs) comprising the engineered nucleic acids (e.g., engineered nucleic acids), engineered cells, compositions comprising the engineered nucleic acids, the recombinant viruses, engineered cells, engineered proteins, chemical agents that are capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, an engineered protein selected from the group consisting of OCT4; KLF4; SOX2; or any combination thereof, an antibody capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, and methods of treating a (e.g., ocular disease), preventing a disease (e.g., ocular disease), regulating (e.g., inducing or inducing and then stopping) cellular reprogramming, regulating tissue repair, regulating tissue regeneration, or any combination thereof).

Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AAV vectors, herpes viral vectors, and retroviral vectors) that encode OCT4; KLF4; SOX2; or any combination thereof that are useful, for example, in inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, or any combination thereof. Also provided herein are recombinant viruses (e.g., lentiviruses, alphaviruses, vaccinia viruses, adenoviruses, herpes viruses, retroviruses, or AAVs) comprising the engineered nucleic acids (e.g., engineered nucleic acids), engineered cells, compositions comprising the engineered nucleic acids, the recombinant viruses, engineered cells, engineered proteins, chemical agents that are capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, an engineered protein selected from the group consisting of OCT4; KLF4; SOX2; or any combination thereof, an antibody capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, and methods of treating a (e.g., ocular disease), preventing a disease (e.g., ocular disease), regulating (e.g., inducing or inducing and then stopping) cellular reprogramming, regulating tissue repair, regulating tissue regeneration, or any combination thereof).

Compositions of retroviruses and methods of using the same for gene delivery, wherein the retroviruses comprise a viral envelope protein comprising at least one mutation that diminishes its native function, a non-viral membrane-bound protein comprising a membrane-bound domain and an extracellular targeting domain.

Provided herein are engineered nucleic acids (e.g., expression vectors, including viral vectors, such as lentiviral vectors, adenoviral vectors, AAV vectors, herpes viral vectors, and retroviral vectors) that encode OCT4; KLF4; SOX2; or any combination thereof that are useful, for example, in inducing cellular reprogramming, tissue repair, tissue regeneration, organ regeneration, reversing aging, or any combination thereof in the central nervous system or ex vivo. Also provided herein are recombinant viruses (e.g., lentiviruses, alphaviruses, vaccinia viruses, adenoviruses, herpes viruses, retroviruses, or AAVs) comprising the engineered nucleic acids (e.g., engineered nucleic acids), engineered cells, compositions comprising the engineered nucleic acids, the recombinant viruses, engineered cells, engineered proteins, chemical agents that are capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, an engineered protein selected from the group consisting of OCT4; KLF4; SOX2; or any combination thereof, an antibody capable of activating expression of OCT4; KLF4; SOX2; or any combination thereof, and methods of treating a disease (e.g., a neurological disease), preventing a disease (e.g., neurological disease), regulating (e.g., inducing or inducing and then stopping) cellular reprogramming, regulating tissue repair, regulating tissue regeneration, or any combination thereof.

To provide novel transduction enhancers and uses thereof.SOLUTION: The present invention relates to a method for transducing a target cell, the method comprising the step of contacting a target cell with a retroviral vector and a compound capable of enhancing transduction efficiency or a combination of such compounds, wherein the target cell is pre- and / or co-stimulated by pre- and / or co-incubation with a transduction enhancing compound or a combination of transduction enhancing compounds prior to and / or during contacting the target cell with the retroviral vector.SELECTED DRAWING: None

Among other things, provided herein are systems that replace the natural random integration activity of a retrovirus with site-specific integration machinery. This approach allows for a more precise targeting of a gene of interest into a human genome, e.g., for therapeutic purposes. The system may include integration-deficient retrovirus (e.g., lentivirus) (IDLV), in which the natural integration activity has been reduced (e.g., by mutation to the viral integrase polypeptide). Instead, the system may comprise a site-specific recombinase (e.g., a serine recombinase, e.g., a serine integrase) capable of directing insertion of a template DNA, or portion thereof, into a desired site in the human genome.

The current disclosure is directed to an immunogenic composition comprising engineered extracellular vesicles with enhanced immunity, methods of making engineered extracellular vesicles with enhanced immunity, a method of slowing or stopping a disease in a subject through the use of the disclosed immunogenic composition, and a method of immunizing a subject through administering the disclosed immunogenic composition.

Provided are a packaging system for packaging a lentiviral vector or a retroviral vector, and a use of the packaging system. Specifically, the provided packaging system comprises a polynucleotide encoding a CAR binding molecule, wherein the CAR binding molecule can bind to a CAR. Pseudotransduction is reduced when a host cell is transduced by the lentiviral vector or the retroviral vector packaged by the provided packaging system, and the ability to transduce a target cell expressing an antigen decreases, thereby significantly improving the targeting performance of the lentiviral vector or the retroviral vector in the transduction of immune cells such as T cells.

The present invention relates to Split-Intron Final Self-Inactivating (SIN) retroviral vectors which comprises a viral major splice donor (mSD) comprising mutations, a mouse mammary tumor vector long terminal repeat (MMTV-LTR) or a Type B leukemogenic virus long terminal repeat (TBLV-LTR), a eukaryotic splice acceptor (eSA), and a eukaryotic splice donor (eSD). Furthermore, the invention relation to the use and methods of uses of such vectors in gene therapy.

Provided herein are immortalized mesenchymal stem cells comprising a replicating recombinant retrovirus. Methods for treating a cell proliferative disorder using these immortalized mesenchymal stem cells are also provided.

The present disclosure belongs to the field of molecular biology, particularly to the technical field of gene analysis and detection, and specifically relates to a method for preparing a DNA library and a method for detecting a retroviral integration site. Specifically, the method for preparing the DNA library comprises the following steps: 1) fragmenting a genomic DNA from a retrovirus-infected cell to obtain DNA fragments; 2) subjecting the DNA fragments to end-repair, A-tailing, and ligation with an adapter to obtain a ligation product, wherein the adapter is an asymmetric double-strand adapter comprising a long-strand sequence and a short-strand sequence, wherein the long-strand sequence sequentially comprises, from a 5' end to a 3' end, a fixed sequence, a random UMI sequence, and an amplification primer binding sequence, and the short-strand sequence comprises a sequence complementary to the fixed sequence; and other steps. The detection method of the present disclosure has extremely high sensitivity, thus having good application potential.

A vaccine for use in the prophylaxis and / or treatment of a diseaseThe present invention relates to an adenoviral vector capable of encoding a virus-like particle (VLP), said VLP displaying an inactive immune-suppressive domain (ISD). The vaccine of the invention shows an improved immune response from either of both of the response pathways initiated by CD4 T cells or CD8 T cells.

The present invention relates to a platform concept for presenting antigenic polypeptides as part of a virus like particle (VLP) construct, which comprises a Gag (group-specific antigen) protein of a beta-retrovirus, for instance of a human endogenous retrovirus K (HERV-K) or of IAPE. Surprisingly it was found that antigenic polypeptide expression in a VLP comprising a Gag protein of HERV-K or of murine endogenous retrovirus IAPE (Intracisternal A-type Particles elements with an Envelope) promotes antigenic polypeptide display and immunogenicity.

The new alpharetrovirus-based particles are suitable for high efficiency of transiently transducing animal cells. e.g. human or murine cells, and which efficiently introduce coding and non-coding RNA contained in the alpharetrovirus-based particles into target cells The alpharetrovirus-based particles also provide for high efficiency of the activity and / or integrity of the RNA that is introduced into the animal cells, as the particles protect the incoming RNA from degradation during entry. The transferred RNA can be of non-coding nature (e.g. single guide (sg) RNA. short-hairpin (sh) RNA. micro RNA. or long non-coding (Inc) RNA. or the RNA may encode proteins or peptides. e.g. receptors. transcription factors. cellular enzymes, antigens for use in vaccination, gene / protein therapy and / or gene editing nucleases, recombinases and transposases.

The present disclosure provides DNA molecules, such as transfer plasmids, useful for manufacturing packaged retroviral vectors encoding a therapeutic protein such as chimeric antigen receptors (CARs) and T cell receptors (TCRs). The encoded retroviral transcript in the DNA molecule includes a transgene, an elongation factor 1-alpha 1 (EFla) promoter, without the EFla intron, operably linked to the transgene and a Rev response element (RRE).

The invention relates to a method for purifying retrovirus, and particularly, the method comprises affinity chromatography, composite mode chromatography and molecular sieve chromatography. The retrovirus purified by the method is high in titer recovery rate, excellent in impurity removal effect, low in requirement on an initial to-be-purified sample and simple in amplification of a purification process, and can be used for large-scale purification of the retrovirus, and the yield and the purity of the retrovirus meet industrial requirements.

The present invention provides a method of electrotransfection-free batch preparation of an immune cell therapeutic product, the CD7 gene of the immune cell itself being knocked out and simultaneously expressing a CD7-targeted chimeric antigen receptor, comprising the production of engineered viroid particles by a stable cell line, the knockout of the CD7 gene in the immune cell using the engineered viroid particles, and the preparation of the therapeutic product of the immune cell, the preparation of the therapeutic product of the immune cell, the preparation of the therapeutic product of the immune cell, and the preparation of the therapeutic product of the immune cell. The CD7 CAR retroviral vector is used for transducing immune cells, so that the immune cell treatment product is obtained. Aiming at the difficulties of high cost, poor universality and high failure risk of CRISPR application electrotransfection technology in current CAR-T cell preparation, the eVLP technology is introduced to carry out efficient and convenient gene editing, so that the safety is guaranteed, the cost is saved, the operation complexity is reduced, and meanwhile, the success rate of immune cell preparation is greatly improved. Based on clinical requirements, a cell therapy product of CD7 KO + CD7 CAR T is jointly constructed by combining a CD7 eVLP vector with a retrovirus of CD7 CAR.

Retroviral vectors with improved stability and that encode receptor-linker-IL-15 (RLI), as well as methods of their use, are provided.

The present disclosure is directed to methods of treating or preventing RNA virus infections and retroviral diseases, such as HIV and AIDS, comprising administering to a subject in need an effective amount of (a) a capsid inhibitor and (b) an adenosine derivative disclosed herein. Compositions comprising an effective amount of an adenosine derivative and an effective amount of a capsid (CA) inhibitor are also provided.

To provide an automated method of producing viral vectors, utilizing engineered viral vector-producing cell lines, or packaging cells, within a fully-enclosed cell engineering system.SOLUTION: A method for automated production of a viral vector, includes: introducing an engineered viral producer cell into a high-temperature chamber of a fully enclosed cell engineering system; transducing the engineered viral producer cell with a vector encoding a gene of interest to produce a transduced viral producer cell; expanding the transduced viral producer cell and producing the viral vector within the cell; transferring the expanded producer cell to a downstream processing module; and isolating the viral vector and purifying the viral vector, the above-described steps being performed in a closed and automated process. Exemplary viral vectors that can be produced include lentivirus vectors, adeno-associated virus vectors, baculovirus vectors and retrovirus vectors.SELECTED DRAWING: Figure 1

The present disclosure relates to methods for determining the magnitude of a subject's immune response against a HIVACAT T-cell immunogen (HTI or “HTI immunogen”) and whether the subject can avoid antiretroviral therapy (ART). These methods are helpful for treating human immunodeficiency virus (HIV) and / or deciding whether to administer, continue or stop antiretroviral therapy in a subject. The present disclosure also relates to antigens, compositions, and kits related to such methods.

The invention belongs to the technical field of biological medicines, and discloses an oligonucleotide molecule for targeted inhibition of a human LINC00921 gene, a coding oligopeptide and application of the oligonucleotide molecule in treatment of lung adenocarcinoma. The invention also discloses application of related drugs or products taking the oligonucleotide molecule for targeted inhibition of the human LINC00921 gene as an active ingredient in inhibition or treatment of lung adenocarcinoma. A specific siRNA target sequence is designed aiming at a target gene, a retrovirus vector plasmid containing the target sequence is successfully constructed through genetic engineering, a recombinant retrovirus capable of efficiently silencing the LINC00921 gene is obtained, the mRNA expression level of the LINC00921 gene in lung adenocarcinoma cells can be remarkably reduced, the gene knock-down effect is outstanding, and the retrovirus can be applied to lung adenocarcinoma cells. The compound has a remarkable inhibition effect on proliferation, migration and invasion ability of lung adenocarcinoma cells. Therefore, the invention has important application value in treatment of lung adenocarcinoma, and has high-throughput operability and good repeatability.

The invention provides application of overexpressed CDCA5 in preparation of a medicine for enhancing the anti-tumor function of T cells, and relates to the technical field of cellular immunotherapy. According to the method for overexpressing the CDCA5, a CDCA5 overexpression agent is used, the CDCA5 overexpression agent is a carrier for overexpressing the CDCA5, and the carrier for overexpressing the CDCA5 is any one of lentivirus and retrovirus. The invention overcomes the defects of the prior art, verifies that the CAR-T overexpressing CDCA5 obviously enhances the anti-tumor function in vivo and in vitro, and provides a new technical direction for anti-tumor treatment.

The application belongs to the technical field of biological medicine, and discloses application of a MYLK3 gene inhibitor in preparation of a drug for treating castration-resistant prostate cancer. The biological function of MYLK3 in prostate cancer is confirmed for the first time, an intervention means with the gene as a target point is provided, and it is confirmed that the MYLK3 inhibitor can improve the sensitivity of castration-resistant prostate cancer to androgen receptor antagonists. A gene therapy drug with the human MYLK3 gene as a treatment target point is specially provided, which is suitable for the treatment of prostate cancer (especially castration-resistant prostate cancer), and can also be combined with other targeted drugs to improve the treatment effect. By designing a reasonable RNAi target sequence for the target gene, a retrovirus vector plasmid containing the target sequence is successfully constructed, which has a significant inhibitory effect on the proliferation ability of prostate cancer cells, and significantly increases the sensitivity of prostate cancer cells to AR antagonists.

The present disclosure relates to a kit and a method for purifying retrovirus, which comprises a reagent combination for purifying retrovirus, comprising a first eluent, a second eluent, an elution liquid and a polyanion compound. By using the purification chromatography combination and method of the present disclosure, the viral load can be increased, the chromatography recovery rate of retrovirus is increased by 2-3 times, reaching 80% and above; at the same time, the impurity level in the virus elution liquid is significantly reduced, such as the residual amount of HCP, which can be reduced by 2-3 times; the eluted retrovirus elution liquid can be stored for 24 hours without losing the infection activity under high salt conditions without adding other special protection reagents; after elution, the next step of ultrafiltration dialysis can be directly carried out without the step of dilution and then concentration, effectively simplifying the operation steps and shortening the processing time.

The current disclosure is directed to an immunogenic composition comprising engineered extracellular vesicles with enhanced immunity, methods of making engineered extracellular vesicles with enhanced immunity, a method of slowing or stopping a disease in a subject through the use of the disclosed immunogenic composition, and a method of immunizing a subject through administering the disclosed immunogenic composition.

To provide a safe and effective mutated woodchuck post-transcriptional regulatory element (WPRE) for use in a retroviral vector.SOLUTION: Provided is a vector comprising a mutated woodchuck post-transcriptional regulatory element (WPRE), wherein the vector does not include an X protein promoter, and the mutated WPRE does not include an X protein open reading frame (ORF).SELECTED DRAWING: None

The invention provides a method for producing engineered virus-like particles through a stable cell line and the engineered virus-like particles of the method, and particularly relates to a method for producing engineered virus-like particles through a stable cell line. The method comprises the following steps: constructing a BaEV retrovirus stable packaging cell line, transfecting a Gag-Cas9 plasmid to the BaEV retrovirus stable packaging cell line obtained in the step 1, constructing a self-inactivation delivery plasmid for a retrovirus packaging system, and selecting to obtain a stable cell line capable of producing engineering viroid particles, therefore, engineered virus-like particles can be produced through a stable cell line. According to the present invention, the eVLP stable cell line preparation method is innovatively developed, the existing production bottleneck is broken through, the stable, efficient and economic gene editing carrier solution is provided for scientific research and clinic, and the further development of the gene therapy field is promoted.

The present disclosure relates to methods of treating or preventing RNA viral infections and retroviral diseases such as HIV and AIDS comprising administering to a subject in need thereof an effective amount of (a) a capsid inhibitor and (b) an adenosine derivative disclosed herein. Also provided are compositions comprising an effective amount of an adenosine derivative and an effective amount of a capsid (CA) inhibitor.

Disclosed herein are compositions of retroviruses and methods of using the same for gene delivery, wherein the retroviruses comprise a viral envelope protein comprising at least one mutation that diminishes its native function, a non-viral membrane-bound protein comprising a membrane-bound domain and an extracellular targeting domain.