Abstract: Nucleic acids are described that encode for triggering receptor expressed on myeloid cells 2 (TREM2) and that can be used in expression constructs, vectors and gene therapies. Also described are methods of using the same for the treatment of TREM2-associated diseases and disorders, especially neurological diseases such as Alzheimer's Disease (AD), Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) or Nasu-Hakola Disease (NHD).

Abstract: The disclosure relates, in some aspects, to compositions and methods for treatment of neurodegenerative disease, for example Alzheimer's disease. In some embodiments, the disclosure provides expression constructs comprising a transgene encoding an APOE Christchurch (e.g., APOE3ch and/or APOE2ch) protein isoform or a portion thereof, an inhibitory nucleic acid targeting an APOE gene or a portion thereof, or any combination of the foregoing. In some embodiments, the disclosure provides methods of treating Alzheimer's disease by administering an expression construct to a subject in need thereof.

Abstract: Aspects of the application relate to compositions and methods for treating spinal muscular atrophy in a subject. In particular, this application provides therapeutic combinations of a recombinant nucleic acid that encodes the survival of motor neuron 1 (SMN1) protein (e.g., in a viral vector), and an antisense oligonucleotide (ASO) that increases full-length survival of motor neuron 2 (SMN2) mRNA (e.g., that is targeted to a nucleic acid molecule encoding the survival of motor neuron 2 (SMN2) and that promotes the inclusion of exon 7 in SMN2 mRNA).