Fondazione Telethon

Fondazione Telethon Ets

University of Pennsylvania

University of California

University of Iowa Research Foundation

Alberto Auricchio

Markus Hildinger

James M Wilson

Enrico Maria Surace

Pasqualina Colella

Ivana Trapani

Beverly L Davidson

Yong Hong Chen

Andrea Ballabio

Gal Bitan

Alessandro Fraldi

Antonio Monaco

Manel Llado Santaeularia

The present invention relates to a method of integrating an exogenous DNA sequence into a genome of a cell comprising contacting the cell with: a) a donor nucleic acid comprising: —at least one STOP codon and a translation initiation sequence (TIS) or—a ribosomal skipping sequence, and—said exogenous DNA sequence wherein said donor nucleic acid is flanked at 5' and 3′ by inverted targeting sequences; b) a complementary strand oligonucleotide homologous to the targeting sequence and c) a nuclease that recognizes the targeting sequence.

Genome editing methods and constructs

The present invention relates to constructs, vectors, relative host cells and pharmaceutical compositions which allow an effective gene therapy, in particular of genes larger than 5 Kb.

Effective delivery of large genes by dual AAV vectors

In various embodiments methods for the treatment and/or prophylaxis of lipofuscin-related disorders are provided. In certain embodiments the methods involve administration of an effective amount of a molecular tweezers to a subject in need thereof.

Inhibition of lipofuscin aggregation by molecular tweezers

The present disclosure provides targeting peptides and vectors containing a sequence that encodes targetting peptides that deliver agents, to the eye. The present inventors have discovered peptides that function to target agents, such as viral vectors, to ocular cells. The present disclosure describes a method to utilize these novel peptides to direct, for example, viral capsids to the cell type of interest. In this instance, ocular cells (such as retinal cells) are targeted by the identified peptides. Vectors harboring capsid proteins modified to include such peptides can be used to provide therapeutic agents to the eye.

Methods and compositions for treating genetic eye diseases

There are disclosed methods and compositions for recovering or improving visual function in a mammal, by means of adeno-associated viral vectors suitable for gene delivery to mammalian retina.

Methods and compositions for recovering or improving visual function

The present invention concerns the use of compounds that interfere with the hedgehog signaling pathway for the manufacture of a medicament for preventing, inhibiting, and/or reversing ocular diseases related with ocular neovascularization. Particularly, the above-mentioned diseases are (wet) age-related macular degeneration, (proliferative) diabetic retinopathy, neovascular glaucoma, retinal vein occlusion, or retinopathy of prematurity (ROP).

Use of compounds that interfere with the hedgehog signaling pathway for the manufacture of a medicament for preventing, inhibiting, and/or reversing ocular diseases related with ocular neovascularization

A method for isolating, from a mixture, a virus having a surface protein with a binding site for sialic acid is provided. The method involves contacting the mixture with mucin which has been linked to a solid support and washing the solid support to remove material from the mixture is non-specifically bound to the mucin-linked support. Thereafter, the specifically bound virus (e.g., AAV4 or AAV5) may be removed in a further washing step utilizing a concentrated slat or solution with low pH. Also described are pharmaceutical kits containing solid supports linked to mucin for use in isolating virus having a surface protein with a binding site for sialic acid, or detecting the presence of the virus in a biological sample.

Method for purification of viral vectors having proteins which bind sialic acid

A pseudotyped rAAV is described, which contains sequences derived from AAV5. A method for producing rAAV pseudotyped with AAV5 capsid is described in which the rep proteins of the serotype or any cross-reactive serotype of the AAV ITRs are utilized. A similar method may be provided to generate a pseudotyped rAAV in which minigenes carrying AAV5 ITRs are packaged in capsids of a heterologous AAV serotype. Also provided are pharmaceutical compositions containing the pseudotyped rAAV and methods of using them for gene delivery.

Growing community of inventors

Naples, Italy

Alberto Auricchio