A red blood cell extracellular vesicle (RBCEV) loaded with a nucleic acid cargo; method for preparing the loaded vesicle; and the therapeutic use of the vesicle thereof are disclosed. The nucleic acid cargoes may be DNA or RNA, single stranded or double stranded, as well as linear or circular.

Disclosed are methods for treating neurological disorders such as Parkinson's disease (PD) using glutamic acid decarboxylase (GAD) and identifying PD patients that will be most receptive to the method of treating PD. In one aspect, the disclosure provides a method of treating PD in a subject in need thereof, the method comprising: (a) identifying a subject having less than about 10 hours, and preferably less than about 8 hours, of on-time per day; and (b) administering to the subject a composition comprising a therapeutically effective amount of one or more vectors to the subthalamic nucleus of the patient, wherein each vector comprises a nucleic acid sequence encoding glutamic acid decarboxylase (GAD) and wherein the subject's on-time is increased.

Disclosed herein are engineered AAV VP capsid polypeptides with the ability to assemble into virus particles and having improved tissue tropism to, for example, CNS tissues. The capsids are engineered using the high throughput discovery system described herein. In certain embodiments, provided herein are recombinant adeno-associated virus (AAV) VP capsid polypeptides having at least one mutation in a residue corresponding to residue 581 to residue 589 in SEQ ID NO: 1.

The present invention relates to lentiviral particles which have been pseudotyped with Nipah virus (NiV) fusion (F) and attachment (G) glycoproteins (NiVpp-F/G). Additionally, the present invention relates to truncated NiV-F glycoproteins useful in producing such NiVpp lentiviral particles, as well as to additional variant peptides which enhance activity. Further, the present invention relates to methods of using such lentiviral particles or sequences, for example in the treatment of cancer or CNS disorders.

In some aspects, fusosome compositions and methods are described herein that comprise membrane enclosed preparations, comprising a fusogen. In some embodiments, the fusosome can the target cell, thereby delivering complex biologic agents to the target cell cytoplasm.

Disclosed herein are methods of repairing or restoring a sarcoglycan complex or DAPC, stabilizing DAPC, restoring DAPC function, or increasing or enhancing expression of one or more components of a sarcoglycan complex or DAPC in a subject suffering from a muscular dystrophy.

Disclosed are nanoparticles comprising an end-modified poly(β-amino ester) and an additive that is a sugar or sugar derivative, such as a sugar, a sugar alcohol or chitosan. The nanoparticles may be used in any field where polymers have been found useful, including in medical fields, particularly in drug delivery. The polymers are useful in delivering a polynucleotide such as DNA, RNA or siRNA, a small molecule or a protein. Also disclosed are compositions comprising said nanoparticles and an active agent, methods for preparing said nanoparticles, said nanoparticles and compositions for use in medicine, and in vitro methods using said nanoparticles and compositions.

Disclosed herein are nanoparticle compositions including an mRNA and a lipid component and methods of using the same. The present invention provides compositions and methods involving lipid-containing nanoparticle compositions to deliver mRNA to cells. In one aspect, the invention provides a nanoparticle composition including (i) a lipid component including a phospholipid (which may or may not be unsaturated), a PEG lipid, a structural lipid, and a compound of formula (I) and (ii) an mRNA encoding a polypeptide of interest.

The present disclosure provides zinc finger fusion proteins that inhibit expression of the prion gene in the nervous system, and methods of using the proteins to treat prion disease.

Compositions comprising nanoparticles, nanoplexes or virus comprising isolated nucleic acid comprising nucleic acid encoding a mammalian, and methods of using the compositions, are provided.