The present application provides materials and methods for treating a patient with a titin-based myopathy, particularly a titin-based cardiomyopathy, and/or other titinopathy. In addition, the present application provides materials and methods for editing the titin gene in a cell by genome editing.

The instant invention provides for novel catiomc lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with oligonucleotides. It is an object of the instant invention to provide a cationic lipid scaffold that demonstrates enhanced efficacy along with lower liver toxicity as a result of lower lipid levels in the liver. The present invention employs low molecular weight cationic lipids with one short lipid chain to enhance the efficiency and tolerability of in vivo delivery of siRNA.

The instant invention provides for novel catiomc lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with oligonucleotides. It is an object of the instant invention to provide a cationic lipid scaffold that demonstrates enhanced efficacy along with lower liver toxicity as a result of lower lipid levels in the liver. The present invention employs low molecular weight cationic lipids with one short lipid chain to enhance the efficiency and tolerability of in vivo delivery of siRNA.

Poly(amine-co-ester) polymers, methods of forming active agent-load polyplexes and particles therefrom, and methods of using them for delivery of nucleic acid agents with optimal uptake have been developed. Examples demonstrate critical molecular weights in combination with exposed carboxylic and/or hydroxyl groups, and methods of making. Typically, the compositions are less toxic, more efficient at drug delivery, or a combination thereof compared to a control other transfection reagents. In some embodiments, the compositions are suitable for in vivo delivery, and can be administered systemically to a subject to treat a disease or condition. For poly(amine-co-ester) polymers with specific amine or hydroxyl group containing end-groups in admixture with PEGylated poly(amine-co-ester) polymers, in vivo delivery to the lung by inhalation has been shown.

The disclosure provides, e.g., compositions and methods for modulating a host response to a Gene Writer system. In some embodiments, modulation of the host response results in increased integration of a heterologous nucleic acid sequence of interest into a target genome. In some embodiments, modulation of the host response results in an increased stability, e.g., maintenance of an insertion or expression thereof. In some embodiments, modulation of the host response results in decreased cytotoxicity.

The disclosure provides, e.g., compositions and methods for modulating a host response to a Gene Writer system. In some embodiments, modulation of the host response results in increased integration of a heterologous nucleic acid sequence of interest into a target genome. In some embodiments, modulation of the host response results in an increased stability, e.g., maintenance of an insertion or expression thereof. In some embodiments, modulation of the host response results in decreased cytotoxicity.

Biodegradable particles for delivering a nucleic acid encoding gene-editing factors or a nucleic acid associated with a therapeutic protein to a cell, and compositions, methods, systems, and kits for gene editing in vivo or ex vivo or gene therapy for treating retinal eye diseases are disclosed.

Biodegradable particles for delivering a nucleic acid encoding gene-editing factors or a nucleic acid associated with a therapeutic protein to a cell, and compositions, methods, systems, and kits for gene editing in vivo or ex vivo or gene therapy for treating retinal eye diseases are disclosed.

The present disclosure relates to antigen presenting cells and uses thereof for treating sepsis. In some aspects, disclosed herein is an antigen presenting cell, comprising: a lipid-based nanoparticle, comprising: a recombinant polynucleotide, comprising: a first nucleic acid encoding an antimicrobial peptide; a second nucleic acid encoding cathepsin B; and a third nucleic acid encoding a linker; and a vitamin-lipid.

The present invention relates to compositions comprising a delivery vehicle conjugated to a targeting domain, wherein the delivery vehicle comprises at least one agent, and wherein the targeting domain specifically binds to an CD4.sup.+ T cell antigen. The invention also relates to methods of treating or preventing diseases and disorders, including cancers, infectious diseases, and immunological disorders, using the described compositions.