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Gene Therapy

Delivery of Genes for Diseases and Beyond.

What is gene therapy? Gene therapy is a method that introduces new genes into a variety of cells that are in need of a new genetic function or gene alteration by use of DNA modifying agents. Gene therapy can correct, delete, or edit preexisting genes, the fundamental building block of life. In a genome, these edits can help alter disease processes or give rise to a new physiological function that was not previously present in that cell. New development at the UMassMed Horae Gene Therapy Center.




Browse Our Inventions!



Title: Screening Novel Clinical Vectors Packaged with Naturally Occurring AAV Capsid Variants from the Human Population with Desired Tissue Tropisms and Properties. UMMS16-71. Patent Pending.

  • The current invention discloses AAV genome sequences that were isolated from normal and diseased human tissue. A novel approach to extract AAV variants allowed for detection of diversity of viral genome. Cap sequences have been determined from the isolates from human biopsies, and include five tissue types and four tumor types. The aggregation of naturally occurring AAV2 and AAV2/3 hybrid variants are unique and have a novel tropism profile suited for tissue targeting purposes.

Title: AAV2-mediated Gene Delivery of sFasL as a Neuroprotective Therapy in Glaucoma. UMMS16-64; Patent Pending.

  • New AAV therapy facilitates long-term production of sFasLin the retina by intra-vitreal injection with no detrimental effect observed in normal animals. Glaucoma-prone mice were injected either before or after disease onset and both animals were found to have preserved retinal ganglion cells with their axons, which normally results in death with onset of the disease. 

Title: Use of miR-122 to Treat Liver Diseases. UMMS16-56; Patent Pending.  

Title: Branched Oligonucleotides as Therapeutics. UMMS16-45; Patent Pending. 

  • This technology is based on the discovery that branched oligonucleotide structure improves the level of tissue retention in brain by more than 100 fold compared to non-branched compounds of identical chemical composition. The invention discloses branched oligonucleotides, specifically di-branched assymetric fully modified siRNAs, exhibiting great uniform distribution throughout the CNS and other target tissues, enhanced cellular uptake, minimal immune response and off-target effects, without formulation. 

Title: CARDS: CRISPR Arrayed Repeat Detection System / Part II. UMMS16-41; Patent Pending. 

  • This invention provides a means to resolve the 3-D genome in live cells by disclosing a novel CRISPR-based system in which as many as six different genomic loci can be labeling, each in a distinctive color, in live cells. This technology, called "CRISPRainbow" is far more expansive that fluorescence in situ hybridization (FISH) conducted on fixed cells. The invention further discloses methods to track by real-time fluorescence microscopy the assembly dynamics and target residence lifetimes of CRISPR machinery in live cells.  

Title: The Use of Phage anti-CRISPR Proteins for the Control of Cas9 Genome Editing. UMMS16-39; Patent Pending. 

  • This novel “off-switch” for Cas9 is important for preventing off target editing effects from CRISPR technology. This technology consists of proteins that have the ability to inhibit NmeCas9 nuclease. This invention has great potential for application in genome editing with CRISPR in human application. 

Title: A Process for Delivering Small RNAs to Sperm. UMMS16-37; Patent Pending. 

  • This invention provides methods to modulate transgenerational epigenetic inheritance, wherein some epigenetic phenotypes are maintained through generations. The disclosed method involves using epididymosomes, small vesicles found in the testis, to deliver RNA molecules to sperm, enabling tailored RNA delivery to the zygote upon fertilization. 

Title: In vitro and in vivo Transduction of Intact Pre-implantation Mammalian Embryos. UMMS16-29; Patent Pending. 

  • This invention simplifies genetic engineering in mammalian research and commercial settings by introducing nucleic acids into mammalian embryos without the need for conventional mechanical methods, microinjection or electroporation, which can be lethal. The new transgenic platform works simply by exposing AAV viral particles to an “intact” pre-implantation embryo. Using this method minimizes the need for labor-intensive embryo harvesting and transferring into pseudopregnant females. 

Title: Development of Anti-angiogenic miRNA Therapeutics for Corneal Neovascularization. UMMS16-23; Patent Pending. 

  • This new technology includes two novel inventions: 1) discovery of miRNAs that influences the neovascularization of the cornea and 2) optimization of rAAV gene therapy method for specific delivery to the cornea. Neovascularization is the most common corneal pathological condition and underestimated cause of blindness. Injection of the rAAV constructs that include synthetic nucleic acids that mimic or inhibit the discovered miRNA can reduce corneal neovascularization in mice. 

Title: Method to Enhance the Efficiency of Systemic AAV Gene Delivery to the Central Nervous System. UMMS16-19; Patent Pending.

  • This invention relates to compositions and methods for increased efficiency of gene transfer to the CNS. The invention is based on the surprising discovery that viral vector-mediated delivery of nucleic acids to the CNS of a subject can be enhanced by administering the viral vector (rAVV) with a composition comprising a highly hydrophilic molecule conjugated to a blood brain barrier (BBB)-receptor ligand (e.g., K16ApoE). 

Title: Closed-ended Linear Duplex DNA (CELiD) for Non-Viral Gene Transfer: Methods, Materials, and Uses for Therapeutic Gene Transfer. UMMS16-18; Patent Pending.  

  • This invention provides a novel gene delivery vector that elicits little immune response and is not limited in carrying capacity. The invention discloses novel closed-ended linear DNA molecules suitable for long-term gene therapy and methods of delivery. 

Title: Gene Therapy and/or Small Molecule Treatment to Correct Beta-Oxidation and Glycolysis in Neurodegenerative Disorders Involving N-Acetylaspartate (NAA) Metabolism and its Associated Metabolic Pathways. UMMS16-17; Patent Pending.

Title: Gene Therapy and/or Small Molecule Treatment to Correct Beta-Oxidation and Glycolysis in Neurodegenerative Disorders Involving N-Acetylaspartate (NAA) Metabolism and its Associated Metabolic Pathways. UMMS16-17; Patent Pending.

Title: Adeno-associated Virus Serotype Vectors Efficiently Transduce Normal Prostate Tissue. UMMS16-16; Patent Pending.

  • Newly discovered rAAVs that can effectively apply gene therapy to the prostate. With direct local injection of rAAV into the prostate, this technology holds the potential to treat numerous diseases, including prostate cancer, without the need for expensive and painful sugary, radiotherapy and medication. 

Title: Novel Metabolically Stable Oligonucleotide Conjugates. UMMS16-09; Patent Pending. 

  • The invention discloses novel hydrophobically-conjugated oligonucleotides useful for RNA interference. The oligonucleotide conjugates are characterized by efficient RISC entry, minimum immune response and off-target effects, efficient cellular uptake without formulation, and efficient and specific tissue distribution. 

Title: Repairing Compound Heterozygous Recessive Mutations By Allele Exchange. UMMS16-08; Patent Pending. 

  • This new mutation repair innovation builds on a previously existing two steps gene editing system: 1) induce a break in the genome where the disruption is protective and 2) repair this break with known new mutation. The clever new approach focuses on the first step, which could help patients suffering from genetic diseases caused by two mutations located within a single gene (compound mutation). This concept circumvents the need to utilize the second step of the gene editing technology in these compound mutations because the inventors capitalized on the allele exchange process that occurs in a normal biological setting. 

Title: DNase H Activity of Neisseria Meningitidis Cas9. UMMS16-05; Patent Pending. 

  • This new technology capitalizes on the discovery of DNase H activity in NmeCas9 that could serve as a novel programmable RNA-guided "restriction enzyme" that cleaves ssDNA, with no sequence constraints. Compared to RNase H that degrades the RNA strand of a RNA-DNA hybrid (with little or no sequence preference), NmeCas9's DNase activity makes specific cuts and has the opposite nucleic acid specificity, i.e. cleaving the DNA strand of the hybrid duplex. 

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Title: SerpinA1 Null Mouse as a Model for Alpha-one Antitrypsin Deficiency and Lung Conditions. UMMS15-62. Patent Pending. 

  • The invention provides a novel mouse model with alpha-one antitrypsin deficiency for use as a tool to study lung conditions including emphysema. With the use of the recently developed CRISPR technology, the inventors designed and implemented a strategy to delete all five copies of the SerpinA1 gene at once overcoming previous technical limitations preventing development of SerpinA1 null mice. 

Title: Recombinant Glut1 Adeno-associated Viral Vector Constructs and Related Methods for Restoring Glut1 Expression. UMMS15-61; Patent Pending. 

  • This new rAAV gene therapy introduces Glut1, a primary glucose transporter in the blood brain barrier (BBB), to the brain through endothelial cells lining the brain vasculature. Glut1-deficiency syndrome is an autosomal-dominant disorder, a rare but debilitating childhood neurological disorder. Introducing Glut1 using this technology was shown to improve symptoms associated with Glut1 deficiency in mice, demonstrating potential use in patients with Glut1-deficiency syndrome.  

Title: Transgenic Expression of DnaseI in vivo Delivered by an Adeno-associated Virus Vector. UMMS15-38; Patent Pending.

  • This invention uses AAV therapy to deliver an important enzyme, DNaseI, for cyctic fibrosis (CF) treatment. Traditional clinical methods of DnaseI delivery use solely nebulizers, which limit the delivery of the enzyme to the lung. With this new quality-controlled AAV vector for delivery, DnaseI can now be delivered locally to other organ systems affected by CF for more comprehensive disease management. 

Title: Transient Delivery of Designer Nuclease Protein Using Viral Vectors For Safer Gene Editing. UMMS15-34; Patent Pending. 

  • This new technology addresses the fundamental issues arising in the emerging biotechnology of gene editing, off-target effects from prolonged treatment. Specifically, this invention improves the CRISPR gene editing system by delivering its nuclease component Cas9 by using a traditional gene therapy method utilizing AAV. Once nuclease Cas9 is delivered, the Cas9 will slowly degrade and yield a reduction in genotoxicity and undesirable off-target genome editing associated with CRISPR therapy. 

Title: Development of Efficient and Safe rAAV Compatible Silencing Construct. UMMS 15-29; Patent Pending. 

  • This invention spans from the invention of UMMS15-28, an rAAV optimized for compatibility and efficacy for shRNA delivery. This process was tested in UMMS15-28 by examining the regional importance of shRNA within the viral genome. This upgraded shRNA-rAAV delivery system has optimized flanking sequences and shRNA structure. The shRNA backbone has lower loop complementarity, causing lower thermodynamic stability that increases its efficacy. This concept was tested by designing multiple Artificial miRNA (AmiRNA), where AmiRNA have the optimized structure while still possessing the shRNA interfering properties. This mechanism for shRNA deliver is highly efficient and safe for sustained silencing. 

Title: Novel rAAV Genome Designs Using Artificial Hairpin Loop Structures to Replace at least One AAV Inverted Terminal Repeat (ITR). UMMS 15-28; Patent Pending. 

  • This invention capitalizes on the discovery that short hairpin RNA (shRNA) can hinder viral genome replication when specifically placed in relationship to the AAV ITR. To improve the efficacy of AAV-mediated shRNA delivery, the inventors designed and tested multiple rAAV with shRNA placed in different regions of the AAV genome in order to identify the optimal AAV vector for shRNA.

Title: New AAV Vectors for Safe and Efficient Expression of Lysosomal Enzymes in the CNS. UMMS15-19; Patent Pending. 

  • New AAV vectors that enable transgene expression at therapeutic levels for treatment of lysosomal and other disorders. These levels are achieved without the adverse events that arises due to secondary effects of AAV-mediated product delivery. This newly engineered regulatory element can apply broadly to circumvent adverse effects of AAV therapy.

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Title: Position specific requirements for nucleotide pairing or mismatches between microRNA or small interfering RNA (siRNA) and target RNA to promote occupancy and retention of an Argonaute protein or RNA-induced Silencing Complex (RISC) on a target RNA. UMMS14-70; Patent Pending.

  • This new invention of “tether” oligo allows for siRNA delivery with higher potency and tissue specificity in medical applications. Tethering endogenous miRNAs that are highly tissue specific can direct them to the target mRNA of interest and this nuclease-resistant oligo can robustly increase efficacy of siRNA therapy. Unlike previous methods, this oligo restricts siRNA to specific cell types which may yield reduced off-target effects.

Title: Broadening the Precision and Targeting Range of Cas9 through DNA Binding Domain Fusions and PAM Recognition Mutations. UMMS14-68; Patent Pending.

  • New Cas9 technology with improved activity, precision, and sequence targeting range. This new Cas9 nuclease-DNA targeting unit chimera utilizes programmable DNA binding domain for editing specificity. The chimeric nuclease complex allows for conjugation of other Cas9 variants to reduce off-target and undesired editing of the genome. This improved Cas9 technology will have application for future human gene therapy. 

Title: Novel High Efficiency Library-identified CNS-tropic AAV Vectors. UMMS14-59; Patent Pending.

  • Newly designed recombinant AAV capsids with greater efficiency for CNS delivery than AAV9, the natural variant with the currently highest known CNS transduction efficiency. These new AAV capsids, B1-B4, show considerably lower off-target effects in the liver when compared to AAV9. Additionally, each of these AAV capsids show selectively higher efficiency for specific peripheral tissues (e.g. pancreas, sk. muscle, heart, adipocyte).

Title: Novel High Efficiency Peptide Grafted CNS-tropic AAV Vectors. UMMS14-58; Patent Pending. 

  • New AAV technology with an insertion of 19-amino acid “alanine string” that has dramatically increased CNS tropism compared to that of AAV9, the natural variant with the currently highest known CNS transduction efficiency. This technology shows increased CNS transduction without changing transduction efficiency of peripheral tissues.

Title: Modified Mullerian Inhibiting Substance (MIS) Proteins and Uses Thereof for the Treatment of Diseases. UMMS14-56; Patent Pending.

  • A new recombinant human MIS protein with improved effectivity may improve the treatment of cancer or neurodegenerative disease. This technology maximizes bioactivity using a leader sequence and a modified cleavage site that promotes increased product yield and MIS processing. This recombinant MIS protein also includes a tag to facilitate purification for research and therapeutic purposes.


  • This new invention spans from the discovery of potent silencing site that was previously unidentified on Huntington gene (htt) through screening of more than 200 compounds. Conventional siRNAs will target this 3’ UTR site for potent inhibition. Efficacy was demonstrated using different siRNA configurations in several cell types and primary neurons that may aid research and future therapeutic applications. 

Title: Antisense Oligonucleotides to Restore Dysferlin mRNA and Protein Expression in Dysferlin-deficient Cells. UMMS14-41; Patent Pending.

  • This technology originates from identification of a deep intronic mutation in Dyferlin (DYSF) that alters mRNA splicing to include a mutant peptide fragment within a key DYSF domain. This new antisense oligo nucleotide(AON-)mediated exon-skipping to restore production of normal, full-length DYSF in patients' cells in vitro, offering therapeutic solution for patient with Dyferlin-associated maladies. 

Title: miRNA-mediated Transcriptional Detargeting to Reduce Transgene Immunity. UMMS14-22; Patent Pending.

  • This new AAV technology involves co-delivery of a transgene that minimizes immune responses against the transgene product of interest. Specifically, this process involves administering a rAA-harboring a transgene engineered to express an inhibitory RNA transcript that targets one or more immune- associated miRNA. This interaction lowers the immune response and consequently increases the potency of the therapeutic protein and its effects.

Title: Efficient Exosomal Loading Using Hydrophobically Modified Therapeutic Oligonucleotides. UMMS14-09; Patent Pending.

  • This novel invention discloses a novel RNAi delivery vehicle. Specifically, describing methods of loading exosomes with hydrophobically modified nucleic acids which exhibit a much higher loading efficiency than methods currently used (i.e. electroporation, transfection with cationic lipid reagents, and ultracentrifugation).

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Title: MicroRNA Mediated Knockdown of SOD1 Using Recombinant Adeno-associated Vectors. UMMS13-19; Patent Pending. 

  • This invention discloses a novel miRNA delivered by rAAV for silencing SOD1 & C9orf72 SODl genes, which are associated with ALS. This method enables effective therapy at low doses with the persistence of rAAV episomes that continually expresses the nucleic acids, thus rendering re-treatment unnecessary. This method also minimizes rAAV exposure to non-CNS peripheral tissue.

Title: Peptide-modified Glucagon Particles for Delivery of Therapeutic Cargoes. UMMS13-05; Patent Pending. 

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Title: Critical Amino Acid Residues Contribute to Crossing Vascular Barrier by AAV9 Vector. UMMS12-73; UMMS; Patent Pending. 

  • New rAAV vector technology desirable for gene therapy applications addressing muscular and lung disorders. A novel AAV9 capsid mutant produces local tissue-restricted expression and genome persistence, delivered by intravascular (IV), intramuscular (IM) and intranasal (IN) route. The therapy is effective while producing low levels of expression in liver.


  • The present invention provides silencing vectors that may be useful in "chromosome therapy" for Down syndrome or may be used as a research tool/system to investigate genomic expression changes and the cellular pathology of trisomy 21. This technology is based on the discovery that the imbalanced expression of hundreds of genes across an extra chromosome can be corrected in Down Syndrome patient stem cells by the targeted addition of one gene, XIST, in a specific location.

Title: SRPX FOR TREATMENT OF CANCER. UMMS12-08; Patent 9,290,744.

  • This technology provides compositions and methods of treatment for lung cancer. The invention is based on a discovery the tumor suppressor, SRPX is found at low levels of expression in solid human tumors compared to normal tissue. When SRPX is introduced at sufficient levels to tumor cells, SRPX can induce apoptosis and senescence to inhibit cellular proliferation. SRPX can easily be administered using the AAV gene therapy method and markedly suppresses lung cancer in mice.

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  • Newly designed multicistronic expression construct with efficient shRNA delivery. Hairpin RNAi expression cassette shown to specifically improve replication and packaging efficiency.

Title: Chimpanzee-Derived Novel Natural Variants of AAV9: Vector Development and Interrogation of Correlations Between Capsid Structure and Vector Biology. UMMS10-39; Patent Pending.

  • Novel method to isolate and characterize natural variants of AAV9. This new information allows for designing caspids with higher efficiency in packaging and tissue specificity.


  • New effective and safe gene therapy approach that allows gene delivery across the blood brain barrier (BBB) upon intravascular administration. Designed to minimize off-target effects by incorporation of non-CNS-tissue specific miRNA binding site into the transgene expression cassette.



  • AAV10 vector-based gene therapy for treating ALS with enhanced tropism for neuronal cells. Administration of rAAV encoding inhibitory RNA for superoxide dismutase 1 (SOD1) distributes widely throughout CNS with low toxicity. Long-term inhibition of mutant SOD1 improves lifespan in the animal models.

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Title: AAV’S AND USES THEREOF. UMMS09-58; Patent  8,734,8099,284,357.

  • Novel AAVs with tissue targeting capability for application in therapeutic gene therapy and research purposes. With efficient delivery, these AAVs have minimal toxic effects on local tissues. They can also be used to develop somatic transgenic animals with a tissue specific promoter. Additionally, this invention includes composition and a method for isolating other novel AAVs. This technology can be used to express RNAi or RNAi sponge that inhibits one or more RNAi functions in a tissue.


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Title: Isolation of Novel AAV Sequences from Tissue RNAs by Reverse Transcription (RT)-PCR. UMMS08-56; Patent Pending. 

  • This new innovation consists of improvements to the current gene therapy methods using adeno-associated virus. By confronting the issues associated with tissue specificity, the inventors have isolated novel capsid sequences from nonhuman primate tissue that harbor low levels of AAV. The invention discloses a novel method for isolating tissue specific AAV capsid sequences for high efficacy and tissue specificity of AAV that may be valuable in multiple contexts.


  • The technology utilizes methods of implementing viral vectors harboring a transgene(s) in combination with tissue specific anti-miRNA sequences to minimize off-target effects. In addition, this method allows for production of somatic transgenic animal models by targeted destruction of specific cell types.


  • This invention provides a new protocol to describe long range physical interaction of genome loci within and between chromosomes. Long range regulatory elements in the genomes are known to interact. This interaction is important for genome biology, as it can control aspects of the genome, such as stability and dosage compensation. Contrary to the previous methods for describing long range genome interactions, Hi-C does not require prior understanding of one genomic loci, making it a truly genome wide characterization. This invention may reveal important aspects of genomic interaction in disease. 

Title: WFS1: A Master Negative Regulator of Endoplasmic Reticulum Stress Signaling and an Effective Inducer of Insulin-Producing Cells. UMMS08-40; Patent Pending.

  • This new discovery provides a potential therapeutic target for type 1 and 2 diabetes. WFS1 has been identified as a master regulator of the endoplasmic reticulum (ER) stress response pathway and helps maintain ER homeostatsis and consequently protection of beta cell insulin production. High levels of ER stress have been associated with premature death of pancreatic cells. Lentivirus-mediated WFS1 introduction has been developed to convert exocrine cells into insulin-producing cells in patients with type 1 and 2 diabetes. This innovation application may also prove to be beneficial to other diseases that arise from ER including neurodegenerative diseases.