Disclosed are nanoparticles comprising an end-modified poly(β-amino ester) and an additive that is a sugar or sugar derivative, such as a sugar, a sugar alcohol or chitosan. The nanoparticles may be used in any field where polymers have been found useful, including in medical fields, particularly in drug delivery. The polymers are useful in delivering a polynucleotide such as DNA, RNA or siRNA, a small molecule or a protein. Also disclosed are compositions comprising said nanoparticles and an active agent, methods for preparing said nanoparticles, said nanoparticles and compositions for use in medicine, and in vitro methods using said nanoparticles and compositions.

Genetically modified mesenchymal stem cells can be used as a medicament in the treatment of medical conditions associated with inflammation and/or an unwanted immune response in subjects without an alpha1-antitrypsin (AAT) deficiency. The stem cells include an exogenous nucleic acid, which includes (i) an Alpha-1 antitrypsin (AAT) encoding region operably linked to (ii) a promoter or promoter/enhancer combination.

The present invention provides for the intratumoral delivery of immunomodulators. In particular, it provides delivery of co-stimulatory molecules using intratumoral electroporation. The present invention provides a method for the treatment of malignancies, wherein the administration of a plasmid encoding for a therapeutic costimulatory protein, in combination with electroporation has a therapeutic effect on primary tumors as well as distant tumors and metastases.

The present invention relates to compositions and methods for the inhibition of the infectivity of a herpesvirus. In certain embodiments, the compositions and methods provide a CRISPR-associated peptide and a guide nucleic acid, which induce the mutation of herpesvirus genome, thereby inhibiting the infectivity of the herpesvirus. Further disclosed are Cas peptides including Cas9 or a variant thereof comprising one or more point mutations relative to wildtype Streptococcus pyogenes Cas 9 (spCas9), and Cpf1 or a variant thereof.

The present invention provides AAV capsid proteins comprising a modification in the amino acid sequence and virus capsids and virus vectors comprising the modified AAV capsid protein. The invention also provides methods of administering the virus vectors and virus capsids of the invention to a cell or to a subject in vivo.

Disclosed herein are nanoparticle compositions including an mRNA and a lipid component and methods of using the same. The present invention provides compositions and methods involving lipid-containing nanoparticle compositions to deliver mRNA to cells. In one aspect, the invention provides a nanoparticle composition including (i) a lipid component including a phospholipid (which may or may not be unsaturated), a PEG lipid, a structural lipid, and a compound of formula (I) and (ii) an mRNA encoding a polypeptide of interest.

Compositions and methods for down-regulating genes through oral administration of RNAi molecule encapsulated in plant cells are provided.

Circular nucleic acid vectors that provide for persistently high levels of protein expression are provided. The circular vectors of the subject invention are characterized by being devoid of expression-silencing bacterial sequences, where in many embodiments the subject vectors include a unidirectional site-specific recombination product hybrid sequence in addition to an expression cassette. Also provided are methods of using the subject vectors for introduction of a nucleic acid, e.g., an expression cassette, into a target cell, as well as preparations for use in practicing such methods. The subject methods and compositions find use in a variety of different applications, including both research and therapeutic applications. Also provided is a highly efficient and readily scalable method for producing the vectors employed in the subject methods, as well as reagents and kits/systems for practicing the same.

The present invention relates generally to a population of cells genetically modified to produce insulin in a glucose responsive manner and uses thereof. More particularly, the present invention relates to a population of cells genetically modified to produce insulin in response to physiologically relevant levels of glucose and uses thereof. The cells of the present invention are useful in a wide variety of applications, in particular in the context of therapeutic and prophylactic regimes directed to the treatment of diabetes and/or the amelioration of symptoms associated with diabetes, based on the transplantation of the cells of the present invention into mammals requiring treatment. Also facilitated is the design of in vitro based screening systems for testing the therapeutic effectiveness and/or toxicity of potential adjunctive treatment regimes.

An optimized coding sequence of human blood clotting factor eight (VIII) and a promoter may be used in vectors, such as rAAV, for introduction of factor VIII, and/or other blood clotting factors and transgenes. Exemplary of these factors and transgenes arc alpha-1-antitrypsin, as well as those involved in the coagulation cascade, hepatocye biology, lysosomal storage, urea cycle disorders, and lipid storage diseases. Cells, vectors, proteins, and glycoproteins produced by cells transformed by the vectors and sequence, may be used in treatment.