The present disclosure relates to compositions and methods for inducing regeneration of periodontal tissue and bone in a subject. In certain aspects, the composition comprises at least one isolated RNA encoding at least one growth factor, or fragment or variant thereof. In one aspect, the composition comprises a nucleoside-modified RNA encoding at least one growth factor, or fragment or variant thereof.

Provided herein are pharmaceutical compositions (e.g., formulations) that can provide for the long-term stability of AAV vectors. Also provided herein are methods of making and using the pharmaceutical compositions. The pharmaceutical compositions provided by the present disclosure generally comprise an AAV, histidine, a stabilizing agent, a salt, and a surfactant.

Disclosed herein include methods, compositions, and kits suitable for use in the delivery of polyribonucleotides and circuits. There are provided, in some embodiments, RNA exporter proteins comprising an RNA-binding domain, a membrane-binding domain, and an interaction domain capable of nucleating self-assembly. Disclosed herein include polynucleotides encoding cargo RNA molecule(s). In some embodiments, a plurality of RNA exporter proteins are capable of self-assembling into lipid-enveloped nanoparticles (LNs) secreted from a sender cell in which the RNA exporter proteins are expressed, thereby generating a population of LNs comprising a fusogen and exported cargo RNA molecule(s).

The present invention relates to a gene delivery complex comprising: a biocompatible polymer backbone; and pegylated lactoferrin connected to the biocompatible polymer backbone by means of a covalent bond. The gene delivery complex is orally administered into an individual, can be absorbed in vivo by means of a lactoferrin receptor, and enables the in vivo delivery of a target gene and the expression thereof.

Compounds are provided having the following structure: ##STR00001##
or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R.sup.1a, R.sup.1b, R.sup.2a, R.sup.2b, R.sup.3a, R.sup.3b, R.sup.4a, R.sup.4b, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, L.sup.1, L.sup.2, a, b, c, d and e are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, compositions comprising the compounds and methods for their use and preparation are also provided.

A hyperbranched polymer includes a hyperbranched, hydrophobic molecular core, respective low molecular weight polyethyleneimine chains attached to at least three branches of the hyperbranched, hydrophobic molecular core, and respective polyethylene glycol chains attached to at least two other branches of the hyperbranched, hydrophobic molecular core. Examples of the hyperbranched polymer may be used to form hyperbranched polyplexes, and may be included in DNA or RNA delivery systems.

Compositions and methods for editing, e.g., introducing double-stranded breaks, within the TTR gene are provided. Compositions and methods for treating subjects having amyloidosis associated with transthyretin (ATTR), are provided.

Methods are disclosed for treating a cone rod homeobox transcription factor (CRX) autosomal dominant retinopathy in a subject. These methods include administering to the subject an effective amount of a nucleic acid molecule comprising a retinal specific promoter operably linked to a nucleic acid molecule encoding a CRX protein. Compositions are disclosed that include an effective amount of a nucleic acid molecule comprising a retinal specific promoter operably linked to a nucleic acid molecule encoding CRX, for use in treating a CRX autosomal dominant retinopathy in a subject. A retinal specific promoter is disclosed that includes the nucleotide sequence of SEQ ID NO: 1.

The present disclosure relates to extracellular vesicles, e.g., exosomes, comprising an AAV and a scaffold protein. In some aspects, the AAV is in the lumen of the extracellular vesicle. In some aspects, the AAV is associated with the luminal surface of the extracellular vesicle. In some aspects, the AAV is associated with the exterior surface of the extracellular vesicle. Also provided herein are methods for producing the exosomes and methods for using the exosomes to treat and/or prevent diseases or disorders.

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.