Filamentous phage as vector-mediated antibody delivery to the brain.

نویسندگان

  • Dan Frenkel
  • Beka Solomon
چکیده

Early diagnosis of Alzheimer's disease is prevented by lack of means to visualize and target beta amyloid plaques in the brains of affected people. There are many methods of detecting amyloid plaques by staining postmortem brain tissue, but none are available for monitoring in living patients. We propose anti-beta amyloid antibodies as a highly specific probe to monitor amyloid plaque formation in living patients. Intranasal administration of filamentous phage as delivery vector of anti-beta amyloid antibody fragment into Alzheimer's APP transgenic mice enables in vivo targeting of beta amyloid plaques. The plaques were co-visualized both by thioflavin-S and fluorescent-labeled anti-phage antibodies in the olfactory bulb and the hippocampus region. The genetically engineered filamentous bacteriophage proved to be an efficient and nontoxic viral delivery vector to the brain, offering an obvious advantage over other mammalian vectors. The ability to image A beta deposits in vivo would arguably provide the most useful diagnostic and monitoring test for early diagnosis of Alzheimer's disease.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Filamentous Bacteriophage Fd as an Antigen Delivery System in Vaccination

Peptides displayed on the surface of filamentous bacteriophage fd are able to induce humoral as well as cell-mediated immune responses, which makes phage particles an attractive antigen delivery system to design new vaccines. The immune response induced by phage-displayed peptides can be enhanced by targeting phage particles to the professional antigen presenting cells, utilizing a single-chain...

متن کامل

Construction of Human Recombinant ScFv Phage Libraries from the Advanced Stages of Breast Carcinoma Patients

Advances in the field of antibody engineering, and the emergence of powerful screening technology such as filamentous phage display allowed to generate fully human antibodies with high affinities against virtually any desired target from immune or even naIve human repertoires. As a result, the immunogenicity problems related to applications of nonhuman based recombinant antibodies as therapeuti...

متن کامل

Cell-specific targeting by engineered M13 bacteriophage expressing VEGFR2 nanobody

Objective(s): Filamentous bacteriophage M13 was genetically engineered to specifically target mammalian cells for gene delivery purpose. Materials and Methods: A vascular endothelial growth factor receptor 2 (VEGFR2)-specific nanobody was genetically fused to the capsid gene III of M13 bacteriophage (pHEN4/3VGR19). A mammalian expression construct containing Cop-green fluorescent protein (Cop-G...

متن کامل

Immunization of Sheep with Phage Mimotopes against Dermatophilosis

Random peptide libraries (RPL) displayed on the surface of filamentous bacteriophages have been extensively used as a tool to map epitopes or to identify antigenic mimics (mimotpoes) of disease-specific monoclonal antibodies or polyclonal sera. These RPL are engineered by the insertion of degenerate oligonucleotides, encoding a specific number of random amino acids, in frame with a bacteriophag...

متن کامل

رنگ‌آمیزی فاژ آنتی‌بادی نوترکیب ضد فیمبریه K99

Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 !mso]> st1":*{behavior:url(#...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Proceedings of the National Academy of Sciences of the United States of America

دوره 99 8  شماره 

صفحات  -

تاریخ انتشار 2002