This disclosure relates to mRNA therapy for the treatment of methylmalonic acidemia (MMA). mRNAs for use in the invention, when administered in vivo, encode methylmalonyl-CoA mutase (MUT). mRNA therapies of the disclosure increase and/or restore deficient levels of MUT expression and/or activity in subjects.

The present disclosure relates to methods and compositions comprising derivatized-chitosan polyplexes reversibly coated with a polyanion-containing block co-polymer for the localized expression of IL-12 in mucosal tissues, preferably in combination with an IFN-1 activator/inducer, for use in cancer immunotherapy.

Proposed are a stabilizer for an adeno-associated virus (AAV) and a method for stabilizing an adeno-associated virus using the same. More particularly, the present disclosure relates to a stabilizer for an adeno-associated virus including a surfactant or albumin, an adeno-associated virus liquid formulation including adeno-associated virus the stabilizer, and a production method for an adeno-associated virus with improved stability. The technology, according to the present disclosure, inhibits excessive aggregation between viruses when producing a gene delivery virus and therapeutic nanoparticles using an adeno-associated virus and forming an additional polyphenol binder for this purpose, thereby maintaining the particle size to an effective size for drug delivery and improving the stability in the liquid phase. Therefore, the technology is expected to be very useful in the field of drug delivery technology for gene therapy.

Provided herein are combination therapies involving co-expression of an E2 subunit of a branched-chain alpha-keto acid dehydrogenase (BCKDH) from a skeletal muscle-targeted rAAV.hDBT vector and a liver-targeted rAAV.hDBT vector. Also provided herein are combination therapies wherein an E1a and/or an E1b subunit of the BCKDH complex is expressed from muscle and/or liver following rAAV-mediated delivery targeted to these tissues. Further provided is a pharmaceutical composition comprising a rAAV as described herein in a formulation buffer, and a method of treating a human subject diagnosed with MSUD.

A lipid composition containing a nucleic acid, wherein the lipid composition comprises a peptide-lipid conjugate, is provided. The peptide of the peptide-lipid conjugates can be from 4 to 52 amino acids in length. Methods of using the lipid composition in the in vivo delivery of nucleic acids are further provided.

Disclosed herein are circular RNA s and transfer vehicles, along with related compositions and methods of treatment. The circular RNAs can comprise group I intron fragments, spacers, an IRES, duplex forming regions, and/or an expression sequence, thereby having the features of improved expression, functional stability, low immunogenicity, ease of manufacturing, and/or extended half-life compared to linear RNA. Pharmaceutical compositions comprising such circular RNAs and transfer vehicles are particularly suitable for efficient protein expression in immune cells in vivo. Also disclosed are precursor RNAs and materials useful in producing the precursor or circular RNAs, which have improved circularization efficiency and/or are compatible with effective circular RNA purification methods.

A multimerization delivery system that can be used to deliver a cargo molecule intracellularly. The multimerization delivery system can achieve high-efficiency endocytosis of a cargo molecule and high-efficiency release thereof from an endocytic vesicle, significantly improving the cytoplasmic delivery efficiency of the cargo molecule. Once the cargo molecule is available in the cytoplasm, the cargo molecule can play any role related thereto. The multimerization delivery system provides an effective means for affecting the biological mechanisms and pathways of cells, and can be used in various fields such as research, treatment, and diagnosis.

The present invention relates to compositions comprising RNA, preferably messenger RNA (mRNA), more preferably self-amplifying RNA (saRNA), and polymers, in particular cationic polymers, such as polyethylenimine (PEI), poly-L-Lysin (PEL), polyvinylamine (PVA) or polyallylamine (PAA), where individual RNA molecules are present in solution. In the formulations, the RNA is preferentially present in the form of monomers, dimers, timers or oligomers, but not as aggregates comprising a large number of RNA molecules per aggregate, in particular large polyplex nanoparticles. The formulations display improved transfection efficacy and they can be used for delivery of RNA to a subject, where they have an improved dose response relationship in comparison to formulations where large aggregates in the form of polyplex nanoparticles are present.

Compositions and methods for treating neurofibromatic disorders are provided herein, such as expressing Merlin protein or a functional fragment thereof from a viral vector.

Bispecific antibodies (bsAbs) have emerged as a class of promising anti-cancer and anti-infection biological drugs. They are capable of killing target cells, either cancer cells or microbe-infected cells, at levels of nanograms per milliliter serum in vivo, about 1e+5 folds more powerful than regular antibodies. To bypass the problems of high cost in production and inconvenience in administration, a logical solution is to use gene therapy vectors to produce them in vivo. In a series of preclinical studies, we have demonstrated that DNA MiniCircle was able to express far above therapeutic levels of bsAB persistently both in the presence as well as the absence of transfection co-factors. As a specific and intended improvement of the claimed invention, an enhanced form of bispecific antibodies incorporating a target cell-effector cell bridging device (BTEC) is additionally disclosed.