The present disclosure provides nucleic acid molecules comprising a first inverted terminal repeat (ITR), a second ITR, and a genetic cassette encoding a target sequence. In some embodiments, the first ITR and/or the second ITR is an ITR of human bocavirus. Also disclosed are methods of using the nucleic acid molecules in gene therapy applications.

The disclosure provides compositions and methods for the preparation, manufacture and therapeutic use of viral vectors, such as adeno-associated virus (AAV) particles having viral genomes encoding one or more antibodies or antibody fragments or antibody-like polypeptides, for the prevention and/or treatment of diseases and/or disorders.

The invention relates to a kit of parts comprising (i) pharmacological chaperones or a pharmaceutically acceptable salt thereof and (ii) a therapeutic acid-alpha glucosidase (GAA) polypeptide or a nucleic acid molecule encoding a therapeutic GAA polypeptide, wherein said pharmacological chaperones are 1-deoxynojirimycin (DNJ) or a derivative thereof and ambroxol (ABX) or a derivative thereof.

Described herein are constructs used for liver-specific expression of a transgene.

Disclosed are methods for performing transcription-dependent directed evolution (TRADE) and novel AAV capsids selected using such methods.

The invention described herein provides a recombinant DNA viral particle comprising a protein shell encapsulating an RNA vector genome, as well as related compositions and uses thereof.

The present disclosure provides recombinant expression vectors for modulating production of polypeptides of interest in a target cell or target cell population. Aspects of the disclosure include recombinant expression vectors having coding sequences encoding portions of a polypeptide of interest, where the coding sequences are flanked by recombinase recognition sites. Also provided are methods for using the recombinant expression vectors as well as a device for monitoring expression of the polypeptide of interest.

Disclosed are nucleic acid vectors comprising a CBh promoter operably linked to a heterologous sequence encoding a G-protein coupled receptor (GPCR). In some embodiments, composition further comprise a sequence encoding an affinity tag, optionally comprising a SNAP polypeptide. In some embodiments, the GPCR comprises a metabotropic glutamate receptor (mGluR), which is optionally, mGluR2. The disclosure also provides compositions and genetically modified cells comprising these vectors. Methods of treatment of retinal diseases and disorders comprising administering compositions, vectors, and cells of the disclosure to a subject in need are also provided.

The invention concerns a multicistronic nucleic acid, in particular an isolated multicistronic nucleic acid, comprising: A) a sequence comprising successively: A1) a sequence encoding the light chain variable domain of an antibody of interest, fused in the frame with A2) a sequence encoding the constant region of the light chain of an immunoglobulin Ig; and B) a sequence comprising successively: B1) a sequence encoding the heavy chain variable domain of said antibody of interest, fused in the frame with B2) a sequence encoding the constant regions of the heavy chain of an immunoglobulin Ig′ in secretory form; B3) an intronic sequence of the gene of the heavy chain of said immunoglobulin Ig′, said intronic sequence comprising an internal 5′ splice site enabling the splicing of said intronic sequence B3) and a secretory-specific poly(A) (p AS) signal from the 3′ terminal exon of said gene; B4) a sequence, in frame with sequence B1), encoding the transmembrane and cytoplasmic domains M1 and M2 of the immunoglobulin Ig′ BCR, wherein said sequence B4) comprises, between the coding sequences of the M1 and M2 domains, an intronic sequence containing a splice site enabling the splicing of said intronic sequence between the M1 and M2 domains coding sequences; and B5) a membrane-anchored specific poly(A) signal (p AM), after the stop codon of the M2 domain, wherein the multicistronic nucleic acid enables the co-expression of the sequences A and B into separate proteins.

Circular RNA and transfer vehicles, along with related compositions and methods are described herein. In some embodiments, the inventive circular RNA comprises group I intron fragments, spacers, an IRES, duplex forming regions, and an expression sequence. In some embodiments, the expression sequence encodes a chimeric antigen receptor (CAR). In some embodiments, circular RNA of the invention has improved expression, functional stability, immunogenicity, ease of manufacturing, and/or half-life when compared to linear RNA. In some embodiments, inventive methods and constructs result in improved circularization efficiency, splicing efficiency, and/or purity when compared to existing RNA circularization approaches.