Peringatan Keamanan

Toxicology studies have not been conducted.

Voretigene neparvovec

DB13932

biotech approved

Deskripsi

Voretigene Neparvovec-rzyl (VN-rzyl) is an adeno-associated virus vector-based gene therapy.^L1094 An adeno-associated virus is a small virus that infects humans and other primates. It is not pathogenic and it causes a very mild immune response. This type of virus is vastly used as vectors for gene therapy because they can infect dividing and quiescent cell integrating just the carried genes into the host genome without fully integrating into the genome.^A31477 An advantage of this adeno-associated virus is the high predictability, unlike retrovirus, as they associate with a specific region of the human cellular genome localized in the chromosome 19. When used in genetic therapy, this virus is modified for the elimination of its negligible integrative capacity by the removal of *rep* and *cap* and the insertion of the desired gene with its promoter between the inverted terminal repeats.^A31478 VN-rzyl was developed by Spark Therapeutics Inc. and FDA approved on December 19, 2017.^L1095

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler

Obat Target Gen Interaksi Enzim Transporter Carrier

Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

1. Pendahuluan & Konsep

Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).

2. Sumber Data (Validasi)

Data Obat: Diekstraksi dari elemen drugbank-id dan name pada skema XML DrugBank.
Target Protein: Diambil dari elemen targets/target yang memuat polipeptida sasaran.
Genetik: Disinkronisasi dari sub-elemen gene-name dan varian snp-effects.
Genetik: Jumlah titik node dibatasi pada maksimal 10 (Slice=10) interaksi untuk menghindari tumpukan data.

3. Algoritma Visualisasi

Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.

4. Legenda Visual

Obat Utama (Pusat Analisis)

Target Protein (Mekanisme)

Gen (Faktor Genetik)

Metode ini mendukung analisis Precision Medicine dan evaluasi risiko Drug-Drug Interaction (DDI).

Profil Farmakokinetik

Waktu Paruh (Half-Life) Based on the pharmacokinetic preclinical studies performed with VN-rzyl and previous studies with different AAVV, it is possible to determine that the half-life of VN-rzyl is approximately 1.7 hours.[A31485]

Volume Distribusi VN-rzyl was shown to be distributed in serum.[FDA label]

Klirens (Clearance) According to the kinetics of AAVV obtained in preclinical trials, VN-rzyl will present a rapid clearance with less than 3% of the administered dose left after 4 hours.[A31485]

Absorpsi

In preclinical studies, it was found a high level of vector DNA sequences in intraocular fluids as anterior chamber fluid or vitreous. Lower levels were detected in optic nerves, optic chiasm, spleen and liver. There was a very small amount found in lymph nodes.^{FDA label}

Metabolisme

Data metabolisme tidak tersedia.

Rute Eliminasi

VN-rzyl is eliminated transiently and at low levels in tears of both, the injected (45%) and non-injected eye (7%) until day 3 post-injection. Most of the drug elimination by the tears happend during day 1 post-injection.^{FDA label}

Interaksi Obat

0 Data

Tidak ada data.

Target Protein

Retinoid isomerohydrolase RPE65

Referensi & Sumber

Artikel (PubMed)

PMID: 19649989
Deyle DR, Russell DW: Adeno-associated virus vector integration. Curr Opin Mol Ther. 2009 Aug;11(4):442-7.
PMID: 2156265
Kotin RM, Siniscalco M, Samulski RJ, Zhu XD, Hunter L, Laughlin CA, McLaughlin S, Muzyczka N, Rocchi M, Berns KI: Site-specific integration by adeno-associated virus. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2211-5.
PMID: 18441370
Maguire AM, Simonelli F, Pierce EA, Pugh EN Jr, Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM, Rossi S, Lyubarsky A, Arruda VR, Konkle B, Stone E, Sun J, Jacobs J, Dell'Osso L, Hertle R, Ma JX, Redmond TM, Zhu X, Hauck B, Zelenaia O, Shindler KS, Maguire MG, Wright JF, Volpe NJ, McDonnell JW, Auricchio A, High KA, Bennett J: Safety and efficacy of gene transfer for Leber's congenital amaurosis. N Engl J Med. 2008 May 22;358(21):2240-8. doi: 10.1056/NEJMoa0802315. Epub 2008 Apr 27.
PMID: 28712537
Russell S, Bennett J, Wellman JA, Chung DC, Yu ZF, Tillman A, Wittes J, Pappas J, Elci O, McCague S, Cross D, Marshall KA, Walshire J, Kehoe TL, Reichert H, Davis M, Raffini L, George LA, Hudson FP, Dingfield L, Zhu X, Haller JA, Sohn EH, Mahajan VB, Pfeifer W, Weckmann M, Johnson C, Gewaily D, Drack A, Stone E, Wachtel K, Simonelli F, Leroy BP, Wright JF, High KA, Maguire AM: Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet. 2017 Aug 26;390(10097):849-860. doi: 10.1016/S0140-6736(17)31868-8. Epub 2017 Jul 14.
PMID: 24858547
van Gestel MA, Boender AJ, de Vrind VA, Garner KM, Luijendijk MC, Adan RA: Recombinant adeno-associated virus: efficient transduction of the rat VMH and clearance from blood. PLoS One. 2014 May 23;9(5):e97639. doi: 10.1371/journal.pone.0097639. eCollection 2014.

Link

Contoh Produk & Brand

Produk: 3 • International brands: 0

Produk

Luxturna

Injection, suspension; Kit • 0.05 mg/1 • Intraocular • US • Approved
Luxturna

Solution • 5000000000000 vg / mL • Intraocular • Canada • Approved
Luxturna

- • 5000000000000 vg/ml • - • EU • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.