This disclosure relates to the field of exosome delivery systems. In particular, compositions comprising adipose-derived exosomes that may be used as a delivery system are encompassed. The exosome delivery system can be used to deliver exogenous cargo such as miRNA and other inhibitory RNAs, as well as proteins, to target cells in a subject.

The present disclosure belongs to the technical field of gene therapy, and specifically relates to a series of lipid compounds as well as lipid vectors, nucleic acid lipid nanoparticle compositions, and pharmaceutical preparations containing the same. The compound having the structure of formula (I) provided by the present disclosure may be used in combination with other lipid compounds to prepare a lipid vector, which exhibits pH responsiveness, has high encapsulation efficiency for nucleic acid drugs, and greatly enhances the in-vivo delivery efficiency of nucleic acid drugs. Moreover, it is possible to select lipid compounds with different structures as lipid vectors to adjust the enrichment of nucleic acid drugs in different organs, thereby having good market application prospect.

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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.

The present invention provides, among other things, methods of treating phenylketonuria (PKU), including administering to a subject in need of treatment a composition comprising an mRNA encoding phenylalanine hydroxylase (PAH) at an effective dose and an administration interval such that at least one symptom or feature of PKU is reduced in intensity, severity, or frequency or has delayed in onset. In some embodiments, the mRNA is encapsulated in a liposome comprising one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids and one or more PEG-modified lipids.

Embodiments of the present application relate to N-acetylgalactosamine-conjugated nucleosides. In particular, the N-acetylgalactosamine is installed on the nucleobase of the nucleosides through a wide variety of linkers. Methods of making N-acetylgalactosamine-conjugated nucleosides are also disclosed herein. N-acetylgalactosamine is a well-defined liver-targeted moiety and N-acetylgalactosamine-conjugated nucleosides may be used in the preparation of targeted delivery of oligonucleotide-based therapeutics.

Disclosed are compositions having mineral crystals and biological molecules for the delivery of the biological materials and methods for preparing mineral crystals having a biologic material.

The present invention provides, among other things, methods of delivering mRNA in vivo, including administering to a subject in need of delivery a composition comprising an mRNA encoding a protein, encapsulated within a liposome such that the administering of the composition results in the expression of the protein encoded by the mRNA in vivo, wherein the liposome comprises a cationic lipid of formula I-c:

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or a pharmaceutically acceptable salt thereof.

Proposed is a nanoparticle complex containing a nanoparticle that ingestible into a cell, and a lipid-based lipid structure bonded to one portion of an outer surface of the nanoparticle and improving a cellular uptake efficiency of the nanoparticle, wherein the nanoparticle contains a first reactive group, the lipid structure contains a second reactive group chemically bonded to the first reactive group of the nanoparticle, the first reactive group and the second reactive group are chemically bonded to each other, and thus the lipid structure is bonded to the nanoparticle.

The present invention belongs to the technical field of gene therapy, and particularly relates to a series of lipid compounds as well as a lipid carrier, nucleic acid lipid nanoparticle composition and pharmaceutical preparation containing the same. A compound having a structure of a formula (I) provided by the present invention can be used for preparing a lipid carrier together with other lipid compounds, and exhibits pH response, and the entrapment efficiency to a nucleic acid drug is high, which greatly improves in-vivo delivery efficiency of the nucleic acid drug; and furthermore, a lipid compound with a specific structure can be chosen as a lipid carrier based on an organ in which the nucleic acid drug needs to be enriched, having a good market application prospect.

The lipid nanoparticle compositions provided herein preferentially deliver and/or transfect the lung. Also provided herein are therapeutic polynucleotides, e.g. TERT mRNA, which may be delivered with the LNP formulations for the treatment of lung disease and fibrosis.