The present invention relates to lentiviral particles which have been pseudotyped with Nipah virus (NiV) fusion (F) and attachment (G) glycoproteins (NiVpp-F/G). Additionally, the present invention relates to truncated NiV-F glycoproteins useful in producing such NiVpp lentiviral particles, as well as to additional variant peptides which enhance activity. Further, the present invention relates to methods of using such lentiviral particles or sequences, for example in the treatment of cancer or CNS disorders.

The present disclosure provides methods and compositions for genetically modifying lymphocytes, for example T cells and/or NK cells. In some embodiments, the methods include reaction mixtures, and resulting cell formulations, that are created using whole blood, or a component thereof that is not a PBMC, and additionally comprise T cells and recombinant retroviral particles having polynucleotides that encode a CAR. In some embodiments, modified lymphocytes are reintroduced into a subject subcutaneously. In some embodiments, polynucleotides that provide T cells the ability to regulate cell survival and proliferation in response to binding to a CAR, are provided.

Chimeric antigen receptors containing CD123 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

Provided herein are nucleic acid molecules that target the BCL11A enhancer functional regions, compositions comprising the nucleic acid molecules and methods for increasing fetal hemoglobin levels in a cell by disrupting BCL11A expression at the genomic level. Also provided herein are methods and compositions relating to the treatment of hemoglobinopathies by reinduction of fetal hemoglobin levels. In particular, the nucleic acid molecules target the +62, +58, and/or the +55 enhancer functional regions.

A method of eliminating the risk of JCV activation in a subject undergoing immunosuppressive therapy, by administering an effective amount of a gene editing composition directed toward at least one target sequence in the JCV genome, cleaving the target sequence in the JCV genome, disrupting the JCV genome, eliminating the JCV infection, eliminating the risk of JCV activation, and treating the subject with an immunosuppressive therapy. A pharmaceutical composition including at least one isolated nucleic acid sequence encoding a CRISPR-associated endonuclease and at least one gRNA having a spacer sequence complementary to a target sequence in a JCV DNA, the isolated nucleic acid sequences being included in at least one expression vector. Pharmaceutical compositions including at least one isolated nucleic acid sequence encoding at least one TALEN, at least one ZFN, and gene editing composition of C2c1, C2c3, TevCas9, Archaea Cas9, CasY.1-CasY.6, CasX, or argonaute protein, which target at least one nucleotide sequence of the JCV genome.

Disclosed are compositions and methods of treating a neurodegenerative disease in an individual. The methods disclose administration of an Integrin α4β1, Very Late Antigen-4 positive neural precursor cell (“VLA4+NPC”) transfected with a lentivirus overexpressing wild type GCase to an individual having a neurodegenerative disorder. The neurodegenerative disease may include lipid storage diseases, for example Gaucher disease, Parkinson's disease (PD), Dementia with Lewy bodies.

The present disclosure relates to methods for producing lentiviral vectors using mammalian cells. Specifically, the methods utilize three plasmids, rather than four, to provide the required packaging elements and transfer vector to a cell, allowing for the production of a large number of lentiviral vectors in mammalian cells, including suspension-based cells. These methods allow for the production of lentiviral vectors that can be tailored to include a specific gene of interest.

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 said transduction enhancing compound or a combination of transduction enhancing compounds prior to and/or during contacting the target cell with the retroviral vector.

We disclose a lentiviral vector, for use in research, clinical, industrial, and other suitable applications. The novel lentiviral vectors disclosed herein introduce numerous novel elements which increase the safety profile of the vector without reducing the efficacy of the system. The novel lentiviral vectors are useful as safe and highly efficient transduction vectors for any application using or benefitting from transduction.

Provided are an improved lentiviral expression vector, a construction method for same, and applications thereof. The plasmid backbone of the lentiviral expression vector is based on pLVX-Puro and is improved via the following steps: a. adding a CMV enhancer and promoter to the upstream of 5′ LTR by means of gene synthesis and subcloning; b. replacing the original 5′ LTR with a new 5′ LTR (SEQ ID NO: 3) of which the length is 181 bps; c. replacing the CMV promoter on an original vector with an EFS promoter; d. deleting a PGK promoter after multiple cloning sites of the original vector and, at the same time, introducing a P2A connection subsequence; e. replacing original resistance against Puro with resistance against a shorter Blasticidin; and f. replacing original 3′ LTR with an LTR (SEQ ID NO: 7) with a partially deleted U3. The lentiviral expression vector acquired by the improvement provides a greater packaging capacity in comparison with pLVX-Puro.